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Cell and Tissue Research

, Volume 343, Issue 2, pp 289–302 | Cite as

Osteoblast physiology in normal and pathological conditions

  • Anna Neve
  • Addolorata Corrado
  • Francesco Paolo CantatoreEmail author
Review

Abstract

Osteoblasts are mononucleated cells that are derived from mesenchymal stem cells and that are responsible for the synthesis and mineralization of bone during initial bone formation and later bone remodelling. Osteoblasts also have a role in the regulation of osteoclast activity through the receptor activator of nuclear factor κ-B ligand and osteoprotegerin. Abnormalities in osteoblast differentiation and activity occur in some common human diseases such as osteoporosis and osteoarthritis. Recent studies also suggest that osteoblast functions are compromised at sites of focal bone erosion in rheumatoid arthritis.

Keywords

Osteoblasts Wnt/β-catenin pathway RANK/RANKL/OPG Osteoporosis Osteoarthritis Rheumatoid arthritis 

References

  1. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R (1997) β-Catenin is a target for the ubiquitin-proteasome pathway. EMBO J 16:3797–3804PubMedCrossRefGoogle Scholar
  2. Ahrens M, Ankenbauer T, Schroder D, Hollnagel A, Mayer H, Gross G (1993) Expression of human bone morphogenetic protein-2 or -4 in murine mesenchymal progenitor C3H10T1/2 cells mesenchymal cell lineages. DNA Cell Biol 12:871–880PubMedGoogle Scholar
  3. Almeida M, Han L, Martin-Millan M, O'Brien CA, Manolagas SC (2007) Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J Biol Chem 282:27298–27305PubMedCrossRefGoogle Scholar
  4. Ambrosetti D, Holmes G, Mansukhani A, Basilico C (2008) Fibroblast growth factor signaling uses multiple mechanisms to inhibit Wnt-induced transcription in osteoblasts. Mol Cell Biol 28:4759–4771PubMedCrossRefGoogle Scholar
  5. Anderson HC (2003) Matrix vesicles and calcification. Curr Rheumatol 5:222–226CrossRefGoogle Scholar
  6. Anderson MA, Maraskovsky E, Bilingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, Du Bose RF, Cosman D, Galibert L (1997) A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390:175–179PubMedCrossRefGoogle Scholar
  7. Asahina I, Sampath TK, Hauschka PV (1996) Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells. Exp Cell Res 222:38–47PubMedCrossRefGoogle Scholar
  8. Aubin JE (2001) Regulation of osteoblast formation and function. Rev Endocr Metab Disord 2:81–94PubMedCrossRefGoogle Scholar
  9. Aubin JE, Liu F (1996) The osteoblast lineage. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of bone biology. Academic Press, San Diego, pp 51–67Google Scholar
  10. Baldock PA, Sainsbury A, Couzens M, Enriquez RF, Thomas GP, Gardiner EM, Herzog H (2002) Hypothalamic Y2 receptors regulate bone formation. J Clin Invest 109:915–921PubMedGoogle Scholar
  11. Banerjee C, McCabe LR, Choi JY, Hiebert SW, Stein JL, Stein GS, Lian JB (1997) Runt homology domain proteins in osteoblast differentiation: AML3/CBFA1 is a major component of a bone-specific complex. J Cell Biochem 66:1–8PubMedCrossRefGoogle Scholar
  12. Baumbach LL, Marashi F, Plumb M, Stein G, Stein J (1984) Inhibition of DNA replication coordinately reduces cellular levels of core and H1 histone mRNAs: requirement for protein synthesis. Biochemistry 23:1618–1625PubMedCrossRefGoogle Scholar
  13. Beil FT, Seitz S, Priemel M, Barvencik F, Von Domuras C, Rueger JM, Amling M, Podoga P (2008) Pathophysiology and pathomorphology of osteoporosis. Eur J Trauma Emerg Surg 6:527–534CrossRefGoogle Scholar
  14. Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, Holmes GB, Dunstan CR, DePaoli AM (2004) A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 19:1059–1066PubMedCrossRefGoogle Scholar
  15. Bellido T, Stahl N, Farruggella TJ, Borba V, Yancopoulos G, Manolagas SC (1996) Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteoblastic cells. J Clin Invest 97:431–437PubMedCrossRefGoogle Scholar
  16. Bellido T, O'Brien CA, Roberson PK, Manolagas SC (1998) Transcriptional activation of the p21(WAF1, CIP1, SDI1) gene by interleukin-6 type cytokines. A prerequisite for their pro-differentiating and anti-apoptotic effects on human osteoblastic cells. J Biol Chem 273:21137–21144PubMedCrossRefGoogle Scholar
  17. Benson BW, Shulman JD (2005) Inclusion of tobacco exposure as a predictive factor for decreased bone mineral content. Nicotine Tob Res 7:719–724PubMedCrossRefGoogle Scholar
  18. Berg KM, Kunins HV, Jackson JL, Nahvi S, Chaudhry A, Harris KA Jr, Malik R, Arnsten JH (2008) Association between alcohol consumption and both osteoporotic fracture and bone density. Am J Med 121:406–418PubMedCrossRefGoogle Scholar
  19. Bertolini DR, Nedwin GE, Bringman TS, Smith DD, Mundy GR (1986) Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature 319:516–518PubMedCrossRefGoogle Scholar
  20. Blair-Levy JM, Watts CE, Fiorentino NM, Dimitriadis EK, Marini JC, Lipsky PE (2008) A type I collagen defect leads to rapidly progressive osteoarthritis in a mouse model. Arthritis Rheum 58:1096–1106PubMedCrossRefGoogle Scholar
  21. Bonewald LF, Johnson ML (2008) Osteocytes, mechanosensing and Wnt signaling. Bone 42:606–615PubMedCrossRefGoogle Scholar
  22. Boyce BF, Hughes DE, Wright KR, Xing L, Dai A (1999) Recent advances in bone biology provide insight into the pathogenesis of bone diseases. Lab Invest 79:83–94PubMedGoogle Scholar
  23. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346:1513–1521PubMedCrossRefGoogle Scholar
  24. Brandao-Burch A, Utting JC, Orriss IR, Arnett TR (2005) Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization. Calcif Tissue Int 77:167–174PubMedCrossRefGoogle Scholar
  25. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260–1268PubMedCrossRefGoogle Scholar
  26. Buckley MJ, Banes AJ, Jordan RD (1990) The effects of mechanical strain on osteoblasts in vitro. J Oral Maxillofac Surg 48:276–283PubMedCrossRefGoogle Scholar
  27. Burgess TL, Qian Y, Kaufman S, Ring BD, Van G, Capparelli C, Kelley M, Hsu H, Boyle WJ, Dunstan CR, Hu S, Lacey DL J (1999) The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. Cell Biol 145:527–538CrossRefGoogle Scholar
  28. Buxton EC, Yao W, Lane NE (2004) Changes in serum receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and interleukin-6 levels in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1-34). J Clin Endocrinol Metab 89:3332–3336PubMedCrossRefGoogle Scholar
  29. Canalis E (2003) Mechanisms of glucocorticoid-induced osteoporosis. Curr Opin Rheumatol 15:454–457PubMedCrossRefGoogle Scholar
  30. Canalis E, Centrella M, McCarthy T (1988) Effects of basic fibroblast growth factor on bone formation in vitro. J Clin Invest 81:1572–1577PubMedCrossRefGoogle Scholar
  31. Canalis E, Pash J, Varghese S (1993) Skeletal growth factors. Crit Rev Eukaryot Gene Expr 3:155–166PubMedGoogle Scholar
  32. Cantatore FP, Corrado A, Grano M, Quarta L, Colucci S, Melillo N (2004) Osteocalcin synthesis by human osteoblasts from normal and osteoarthritic bone after vitamin D3 stimulation. Clin Rheumatol 23:490–495PubMedCrossRefGoogle Scholar
  33. Cantatore FP, Crivellato E, Nico B, Ribatti D (2005) Osteocalcin is angiogenic in vivo. Cell Biol Int 29:583–585PubMedCrossRefGoogle Scholar
  34. Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641–650PubMedCrossRefGoogle Scholar
  35. Carvalho RS, Bumann A, Schaffer JL, Gerstenfeld LC (2002) Predominant integrin ligands expressed by osteoblasts show preferential regulation in response to both cell adhesion and mechanical perturbation. J Cell Biochem 84:497–508PubMedCrossRefGoogle Scholar
  36. Centrella M, McCarthy TL, Canalis E (1988) Tumor necrosis factor-alpha inhibits collagen synthesis and alkaline phosphatase activity independently of its effect on deoxyribonucleic acid synthesis in osteoblast-enriched bone cell cultures. Endocrinology 123:1442–1448PubMedCrossRefGoogle Scholar
  37. Centrella M, Horowitz MC, Wozney JM, McCarthy TL (1994) Transforming growth factor-beta gene family members and bone. Endocr Rev 15:27–39PubMedGoogle Scholar
  38. Chen AE, Ginty DB, Fan CM (2005) Protein kinase A signalling via CREB controls myogenesis induced by Wnt proteins. Nature 433:317–322PubMedCrossRefGoogle Scholar
  39. Cheng SL, Yang JW, Rifas L, Zhang SF, Avioli LV (1994) Differentiation of human bone marrow osteogenic stromal cells in vitro: induction of the osteoblast phenotype by dexamethasone. Endocrinology 134:277–286PubMedCrossRefGoogle Scholar
  40. Chenu C, Colucci S, Grano M, Zigrino P, Barattolo R, Zambonin G, Baldini N, Vergnaud P, Delmas PD, Zallone AZ (1994) Osteocalcin induces chemotaxis, secretion of matrix proteins, and calcium-mediated intracellular signaling in human osteoclast-like cells. J Cell Biol 127:1149–1158PubMedCrossRefGoogle Scholar
  41. Clark B (2008) Normal bone anatomy and physiology. Clin J Am Soc Nephrol 3:131–139CrossRefGoogle Scholar
  42. Colla S, Zhan F, Xiong W, Wu X, Xu H, Stephens O, Yaccoby S, Epstein J, Barlogie B, Shaughnessy JD Jr (2007) The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells. Blood 109:4470–4477PubMedCrossRefGoogle Scholar
  43. Collart D, Ramsey-Ewing A, Bortell R, Lian J, Stein J, Stein G (1991) Isolation and characterization of a cDNA from a human histone H2B gene which is reciprocally expressed in relation to replication-dependent H2B histone genes during HL60 cell differentiation. Biochemistry 30:1610–1617PubMedCrossRefGoogle Scholar
  44. Corrado A, Cantatore FP, Grano M, Colucci S (2005) Neridronate and human osteoblasts in normal, osteoporotic and osteoarthritic subjects. Clin Rheumatol 24:527–534PubMedCrossRefGoogle Scholar
  45. Couchourel D, Aubry I, Delalandre A, Lavigne M, Martel-Pelletier J, Pelletier JP, Lajeunesse D (2009) Altered mineralization of human osteoarthritic osteoblasts is attributable to abnormal type I collagen production. Arthritis Rheum 60:1438–1450PubMedCrossRefGoogle Scholar
  46. Davis MA, Ettinger WH, Neuhaus JM, Hauck WW (1988) Sex differences in osteoarthritis of the knee. The role of obesity. Am J Epidemiol 127:1019–1030PubMedGoogle Scholar
  47. DeFranco DJ, Glowacki J, Cox KA, Lian JB (1991) Normal bone particles are preferentially resorbed in the presence of osteocalcin-deficient bone particles in vivo. Calcif Tissue Int 49:43–50PubMedCrossRefGoogle Scholar
  48. Dempster DW, Cosman F, Parisien M, Shen V, Lindsay R (1993) Anabolic actions of parathyroid hormone on bone. Endocr Rev 14:690–709PubMedGoogle Scholar
  49. Dequeker J, Mohan S, Finkelman RD, Aerssens J, Baylink DJ (1993) Generalized osteoarthritis associated with increased insulin-like growth factor types I and II and transforming growth factor beta in cortical bone from the iliac crest. Possible mechanism of increased bone density and protection against osteoporosis. Arthritis Rheum 36:1702–1708PubMedCrossRefGoogle Scholar
  50. Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, Korb A, Smolen J, Hoffmann M, Scheinecker C, Heide D van der, Landewe R, Lacey D, Richards WG, Schett G (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156–163PubMedCrossRefGoogle Scholar
  51. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747–754PubMedCrossRefGoogle Scholar
  52. Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P, Pottie P (2003) Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum 48:3118–3129PubMedCrossRefGoogle Scholar
  53. Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs B (2003) Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest 111:1221–1230PubMedGoogle Scholar
  54. El Miedany YM, Mehanna AN, El Baddini MA (2000) Altered bone mineral metabolism in patients with osteoarthritis. Joint Bone Spine 67:521–527PubMedCrossRefGoogle Scholar
  55. Elefteriou F (2008) Regulation of bone remodeling by the central and peripheral nervous system. Arch Biochem Biophys 473:231–236PubMedCrossRefGoogle Scholar
  56. Elmquist JK, Bjørbaek C, Ahima RS, Flier JS, Saper CB (1998) Distributions of leptin receptor mRNA isoforms in the rat brain. J Comp Neurol 395:535–547PubMedCrossRefGoogle Scholar
  57. Erices A, Conget P, Rojas C, Minguell JJ (2002) Gp130 activation by soluble interleukin-6 receptor/interleukin-6 enhances osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. Exp Cell Res 280:24–32PubMedCrossRefGoogle Scholar
  58. Ernst M, Heath JK, Rodan GA (1989) Estradiol effects on proliferation, messenger ribonucleic acid for collagen and insulin-like growth factor-I, and parathyroid hormone-stimulated adenylate cyclase activity in osteoblastic cells from calvariae and long bones. Endocrinology 125:825–833PubMedCrossRefGoogle Scholar
  59. Evans DB, Bunning RA, Russell RG (1990) The effects of recombinant human interleukin-1 beta on cellular proliferation and the production of prostaglandin E2, plasminogen activator, osteocalcin and alkaline phosphatase by osteoblast-like cells derived from human bone. Biochem Biophys Res Commun 166:208–216PubMedCrossRefGoogle Scholar
  60. Franzen A, Heinegard D (1985) Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem J 232:715–724PubMedGoogle Scholar
  61. Friedenstein AJ, Chailakhyan RK, Gerasimov UV (1987) Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet 20:263–272PubMedGoogle Scholar
  62. Fujihara S, Yokozeki M, Oba Y, Higashibata Y, Nomura S, Moriyama K (2006) Function and regulation of osteopontin in response to mechanical stress. J Bone Miner Res 21:956–964PubMedCrossRefGoogle Scholar
  63. Gerstenfeld LC, Chipman SD, Glowacki J, Lian JB (1987) Expression of differentiated function by mineralizing cultures of chicken osteoblasts. Dev Biol 122:49–60PubMedCrossRefGoogle Scholar
  64. Gevers G, Dequeker J (1987) Collagen and non-collagenous protein content (osteocalcin, sialoprotein, proteoglycan) in the iliac crest bone and serum osteocalcin in women with and without hand osteoarthritis. Coll Relat Res 7:435–442PubMedGoogle Scholar
  65. Gilbert L, He X, Farmer P, Boden S, Kozlowski M, Rubin J, Nanes MS (2000) Inhibition of osteoblast differentiation by tumor necrosis factor-alpha. Endocrinology 141:3956–3964PubMedCrossRefGoogle Scholar
  66. Giuliani N, Girasole G, Vescovi PP, Passeri G, Pedrazzoni M (1999) Ethanol and acetaldehyde inhibit the formation of early osteoblast progenitors in murine and human bone marrow cultures. Alcohol Clin Exp Res 23:381–385PubMedGoogle Scholar
  67. Glass DA 2nd, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, Karsenty G (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764PubMedCrossRefGoogle Scholar
  68. Globus RK, Patterson-Buckendahl P, Gospodarowicz D (1988) Regulation of bovine bone cell proliferation by fibroblast growth factor and transforming growth factor beta. Endocrinology 123:98–105PubMedCrossRefGoogle Scholar
  69. Goldring MB, Goldring SR (1990) Skeletal tissue response to cytokines. Clin Orthop Relat Res 258:245-278PubMedGoogle Scholar
  70. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Jüppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, Boogaard MJ van den, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML, Osteoporosis-Pseudoglioma Syndrome Collaborative Group (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523PubMedCrossRefGoogle Scholar
  71. Gordon JA, Tye CE, Sampaio AV, Underhill TM, Hunter GK, Goldberg HA (2007) Bone sialoprotein expression enhances osteoblast differentiation and matrix mineralization in vitro. Bone 41:462–473PubMedCrossRefGoogle Scholar
  72. Grano M, Colucci S, Cantatore FP, Teti A, Zambonin ZA (1990) Osteoclast bone resorption is enhanced in the presence of osteoblasts. Boll Soc Ital Biol Sper 66:1051–1057PubMedGoogle Scholar
  73. Grigorie D, Neacşu E, Marinescu M, Popa O (2003) Circulating osteoprotegerin and leptin levels in postmenopausal women with and without osteoporosis. Rom J Intern Med 41:409–415PubMedGoogle Scholar
  74. Gustafsson BI, Thommesen L, Stunes AK, Tommeras K, Westbroek I, Waldum HL, Slørdahl K, Tamburstuen MV, Reseland JE, Syversen U (2006) Serotonin and fluoxetine modulate bone cell function in vitro. J Cell Biochem 98:139–151PubMedCrossRefGoogle Scholar
  75. Harada H, Tagashira S, Fujiwara M, Ogawa S, Katsumata T, Yamaguchi A, Komori T, Nakatsuka M (1999) Cbfa1 isoforms exert functional differences in osteoblast differentiation. J Biol Chem 274:6972–6978PubMedCrossRefGoogle Scholar
  76. Hauschka PV, Lian JB, Cole DEC, Gundberg CM (1989) Osteocalcin and matrix gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047Google Scholar
  77. Hayashi K, Yamaguchi T, Yano S, Kanazawa I, Yamauchi M, Yamamoto M, Sugimoto T (2009) BMP/Wnt antagonists are upregulated by dexamethasone in osteoblasts and reversed by alendronate and PTH: potential therapeutic targets for glucocorticoid-induced osteoporosis. Biochem Biophys Res Commun 379:261–266PubMedCrossRefGoogle Scholar
  78. Hilal G, Martel-Pelletier J, Pelletier JP, Ranger P, Lajeunesse D (1998) Osteoblast-like cells from human subchondral osteoarthritic bone demonstrate an altered phenotype in vitro: possible role in subchondral bone sclerosis. Arthritis Rheum 41:891–899PubMedCrossRefGoogle Scholar
  79. Hilal G, Massicotte F, Martel-Pelletier J, Fernandes JC, Pelletier JP, Lajeunesse D (2001) Endogenous prostaglandin E2 and insulin-like growth factor 1 can modulate the levels of parathyroid hormone receptor in human osteoarthritic osteoblasts. J Bone Miner Res 16:713–721PubMedCrossRefGoogle Scholar
  80. Hill PA (1998) Bone remodelling. Br J Orthod 25:101–107PubMedCrossRefGoogle Scholar
  81. Hofbauer LC, Schoppet M (2004) Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292:490–495PubMedCrossRefGoogle Scholar
  82. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL (1999) Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140:4367–4370PubMedCrossRefGoogle Scholar
  83. Hopwood B, Tsykin A, Findlay DM, Fazzalari NL (2007) Microarray gene expression profiling of osteoarthritic bone suggests altered bone remodelling, WNT and transforming growth factor-beta/bone morphogenic protein signalling. Arthritis Res Ther 9:R100PubMedCrossRefGoogle Scholar
  84. Horwitz MC, Lorenzo JA (2002) Local regulators of bone: Il-1, TNF, lymphotoxin, interferon-γ, IL-8, Il-10, IL-4, the LIF/IL-6 family, and additional cytokines. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principle of biology. Academic Press, San Diego, pp 961–977Google Scholar
  85. Hoshi K, Komori T, Ozawa H (1999) Morphological characterization of skeletal cells in Cbfa1-deficient mice. Bone 25:639–651PubMedCrossRefGoogle Scholar
  86. Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132:49–60PubMedCrossRefGoogle Scholar
  87. Huang S, Kaw M, Harris MT, Ebraheim N, McInerney MF, Najjar SM, Lecka-Czernik B (2010) Decreased osteoclastogenesis and high bone mass in mice with impaired insulin clearance due to liver-specific inactivation to CEACAM1. Bone 46:1138–1145PubMedCrossRefGoogle Scholar
  88. Ishida Y, Heersche JH (1998) Glucocorticoid-induced osteoporosis: both in vivo and in vitro concentrations of glucocorticoids higher than physiological levels attenuate osteoblast differentiation. J Bone Miner Res 13:1822–1826PubMedCrossRefGoogle Scholar
  89. Ishijima M, Tsuji K, Rittling SR, Yamashita T, Kurosawa H, Denhardt DT, Nifuji A, Ezura Y, Noda M (2007) Osteopontin is required for mechanical stress-dependent signals to bone marrow cells. J Endocrinol 193:235–243PubMedCrossRefGoogle Scholar
  90. Ji C, Casinghino S, Chang DJ, Chen Y, Javed A, Ito Y, Hiebert SW, Lian JB, Stein GS, McCarthy TL, Centrella M (1998) CBFa(AML/PEBP2)-related elements in the TGF-beta type I receptor promoter and expression with osteoblast differentiation. J Cell Biochem 69:353–363PubMedCrossRefGoogle Scholar
  91. Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M (2001) Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2:1665–1671CrossRefGoogle Scholar
  92. Kapoor D, Jones TH (2005) Smoking and hormones in health and endocrine disorders. Eur J Endocrinol 152:491–499PubMedCrossRefGoogle Scholar
  93. Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, Kioussis D, Kollias G (1991) Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 10:4025–4031PubMedGoogle Scholar
  94. Khosla S (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology 142:5050–5055PubMedCrossRefGoogle Scholar
  95. Khosla S, Arrighi HM, Melton LJ 3rd, O'Fallon AEJ, WM DC, Riggs BL (2002) Correlates of osteoprotegerin levels in women and men. Osteoporos Int 13:394–399PubMedCrossRefGoogle Scholar
  96. Kim CH, Kang BS, Lee TK, Park WH, Kim JK, Park YG, Kim HM, Lee YC (2002) IL-1b regulates cellular proliferation, prostaglandin E2 synthesis, plasminogen activator activity, osteocalcin production, and bone resorptive activity of the mouse calvarial bone cells. Immunopharmacol Immunotoxicol 24:395–407PubMedCrossRefGoogle Scholar
  97. Kodama H, Amagai Y, Koyama H, Kasai S (1982) A new preadipose cell line derived from newborn mouse calvaria can promote the proliferation of pluripotent hematopoietic stem cells in vitro. J Cell Physiol 112:89–95PubMedCrossRefGoogle Scholar
  98. Komori T (2003) Requisite roles of Runx2 and Cbfb in skeletal development. J Bone Miner Metab 21:193–197PubMedGoogle Scholar
  99. Komori T (2010) Regulation of bone development and extracellular matrix protein genes by RUNX2. Cell Tissue Res 339:189–195PubMedCrossRefGoogle Scholar
  100. Komori T, Ozawa H (1999) Morphological characterization of skeletal cells in Cbfa1-deficient mice. Bone 25:639–651PubMedCrossRefGoogle Scholar
  101. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764PubMedCrossRefGoogle Scholar
  102. Krishnan V, Bryant HU, Mcdougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202–1209PubMedCrossRefGoogle Scholar
  103. Kubota T, Michigami T, Ozono K (2009) Wnt signaling in bone metabolism. J Bone Miner Metab 27:265–271PubMedCrossRefGoogle Scholar
  104. Kuhl M, Shedahl LC, Park M, Miller JR, Moon RT (2000) The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet 16:279–283PubMedCrossRefGoogle Scholar
  105. Kwan Tat S, Pelletier JP, Amiable N, Boileau C, Lajeunesse D, Duval N, Martel-Pelletier J (2008a) Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts. Arthritis Rheum 58:3820–3830PubMedCrossRefGoogle Scholar
  106. Kwan Tat S, Pelletier JP, Lajeunesse D, Fahmi H, Lavigne M, Martel-Pelletier J (2008b) The differential expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) in human osteoarthritic subchondral bone osteoblasts is an indicator of the metabolic state of these disease cells. Clin Exp Rheumatol 26:295–304PubMedGoogle Scholar
  107. Lacey DL, Grosso LE, Moser SA, Erdmann J, Tan HL, Pacifici R, Villareal DT (1993) IL-1-induced murine osteoblast IL-6 production is mediated by the type 1 IL-1 receptor and is increased by 1, 25 dihydroxyvitamin D3. J Clin Invest 91:1731–1742PubMedCrossRefGoogle Scholar
  108. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176PubMedCrossRefGoogle Scholar
  109. Lajeunesse D, Reboul P (2003) Subchondral bone in osteoarthritis: a biologic link with articular cartilage leading to abnormal remodeling. Curr Opin Rheumatol 15:628–633PubMedCrossRefGoogle Scholar
  110. Lalor BC, France MW, Powell D, Adams PH, Counihan TB (1986) Bone and mineral metabolism and chronic alcohol abuse. Q J Med 59:497–511PubMedGoogle Scholar
  111. Leclerc N, Luppen CA, Ho VV, Nagpal S, Hacia JG, Smith E, Frenkel B (2004) Gene expression profiling of glucocorticoid-inhibited osteoblasts. J Mol Endocrinol 33:175–193PubMedCrossRefGoogle Scholar
  112. Lee MH, Javed A, Kim HJ, Shin HI, Gutierrez S, Choi JY, Rosen V, Stein JL, Wijnen AJ van, Stein GS, Lian JB, Ryoo HM (1999) Transient upregulation of CBFA1 in response to bone morphogenetic protein-2 and transforming growth factor beta1 in C2C12 myogenic cells coincides with suppression of the myogenic phenotype but is not sufficient for osteoblast differentiation. J Cell Biochem 73:114–125PubMedCrossRefGoogle Scholar
  113. Lee SK, Lorenzo JA (1999) Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552–3561PubMedCrossRefGoogle Scholar
  114. Li YP, Stashenko P (1992) Proinflammatory cytokines tumor necrosis factor-alpha and IL-6, but not IL-1, down-regulate the osteocalcin gene promoter. J Immunol 148:788–794PubMedGoogle Scholar
  115. Li Y, Bäckesjö CM, Haldosén LA, Lindgren U (2008) IL-6 receptor expression and IL-6 effects change during osteoblast differentiation. Cytokine 43:165–173PubMedCrossRefGoogle Scholar
  116. Lian JB, Stein GS (1995) Development of the osteoblast phenotype: molecular mechanisms mediating osteoblast growth and differentiation. Iowa Orthop J 15:118–140PubMedGoogle Scholar
  117. Lian JB, Tassinari M, Glowacki J (1984) Resorption of implanted bone prepared from normal and warfarin-treated rats. J Clin Invest 73:1223–1226PubMedCrossRefGoogle Scholar
  118. Lian J, Stewart C, Puchacz E, Mackowiak S, Shalhoub V, Collart D, Zambetti G, Stein G (1989) Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression. Proc Natl Acad Sci USA 86:1143–1147PubMedCrossRefGoogle Scholar
  119. Lian JB, Stein GS, Bortell R, Owen TA (1991) Phenotype suppression: a postulated molecular mechanism for mediating the relationship of proliferation and differentiation by fos/jun interactions at AP-1 sites in steroid responsive promoter elements of tissue-specific genes. J Cell Biochem 45:9–14PubMedCrossRefGoogle Scholar
  120. Lian JB, Stein GS, Stein JL, Wijnen AJ van (1999) Regulated expression of the bone specific osteocalcin gene by vitamins and hormones. Vitam Horm 55:443–509PubMedCrossRefGoogle Scholar
  121. Liggett WH, Lian JB, Greenberger JS, Glowacki J (1994) Osteocalcin promotes differentiation of putative osteoclast progenitors from murine long-term bone marrow cultures. J Cell Biochem 55:190–199PubMedCrossRefGoogle Scholar
  122. Lozupone E, Palumbo C, Favia A, Ferretti M, Palazzini S, Cantatore FP (1996) Intermittent compressive load stimulates osteogenesis and improves osteocyte viability in bones cultured "in vitro". Clin Rheumatol 15:563–572PubMedCrossRefGoogle Scholar
  123. Luppen CA, Leclerc N, Noh T, Barski A, Khokhar A, Boskey AL, Smith E, Frenkel B (2003) Brief bone morphogenetic protein 2 treatment of glucocorticoid-inhibited MC3T3-E1 osteoblasts rescues commitment-associated cell cycle and mineralization without alteration of Runx2. J Biol Chem 278:44995–45003PubMedCrossRefGoogle Scholar
  124. Lynch MP, Stein JS, Stein GS, Lian JB (1994) Apoptosis during in vitro bone formation (abstract). J Bone Miner Res 9:S352Google Scholar
  125. MacDonald PN, Dowd DR, Nakajima S, Galligan MA, Reeder MC, Haussler CA, Ozato K, Haussler MR (1993) Retinoid X receptors stimulate and 9-cis retinoic acid inhibits 1, 25-dihydroxyvitamin D3-activated expression of the rat osteocalcin gene. Mol Cell Biol 13:5907–5917PubMedGoogle Scholar
  126. Majeska RJ, Ryaby JT, Einhorn TA (1994) Direct modulation of osteoblastic activity with estrogen. J Bone Joint Surg Am 76:713–721PubMedGoogle Scholar
  127. Malaval L, Wade-Guéye NM, Boudiffa M, Fei J, Zirngibl R, Chen F, Laroche N, Roux JP, Burt-Pichat B, Duboeuf F, Boivin G, Jurdic P, Lafage-Proust MH, Amédée J, Vico L, Rossant J, Aubin JE (2008) Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis. J Exp Med 205:1145–1153PubMedCrossRefGoogle Scholar
  128. Mansell JP, Bailey AJ (1998) Abnormal cancellous bone collagen metabolism in osteoarthritis. J Clin Invest 101:1596–1603PubMedCrossRefGoogle Scholar
  129. Mansell JP, Tarlton JF, Bailey AJ (1997) Biochemical evidence for altered subchondral bone collagen metabolism in osteoarthritis of the hip. Br J Rheumatol 36:16–19PubMedCrossRefGoogle Scholar
  130. Maruotti N, Cantatore FP, Crivellato E, Vacca A, Ribatti D (2007) Macrophages in rheumatoid arthritis. Histol Histopathol 22:581–586PubMedGoogle Scholar
  131. Maruotti N, Corrado A, Grano M, Colucci S, Cantatore FP (2009) Normal and osteoporotic human osteoblast behaviour after 1, 25-dihydroxy-vitamin D(3) stimulation. Rheumatol Int 29:667–672PubMedCrossRefGoogle Scholar
  132. Massicotte F, Lajeunesse D, Benderdour M, Pelletier JP, Hilal G, Duval N, Martel-Pelletier J (2002) Can altered production of interleukin-1beta, interleukin-6, transforming growth factor-beta and prostaglandin E(2) by isolated human subchondral osteoblasts identify two subgroups of osteoarthritic patients? Osteoarthritis Cartilage 10:491–500PubMedCrossRefGoogle Scholar
  133. Massicotte F, Aubry I, Martel-Pelletier J, Pelletier JP, Fernandes J, Lajeunesse D (2006) Abnormal insulin-like growth factor 1 signaling in human osteoarthritic subchondral bone osteoblasts. Arthritis Res Ther 8:R177PubMedCrossRefGoogle Scholar
  134. Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y, Ohki M (1991) t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci USA 88:10431–10434PubMedCrossRefGoogle Scholar
  135. Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T, Sato Y, Nakagawa N, Yasuda H, Mochizuki S, Gomibuchi T, Yano K, Shima N, Washida N, Tsuda E, Morinaga T, Higashio K, Ozawa H (1998) Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem Biophys Res Commun 247:610–615PubMedCrossRefGoogle Scholar
  136. Mlodzik MM (2002) Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation? Trends Genet 18:564–571PubMedCrossRefGoogle Scholar
  137. Mukherjee A, Rotwein P (2009) Akt promotes BMP2-mediated osteoblast differentiation and bone development. J Cell Sci 122:716–726PubMedCrossRefGoogle Scholar
  138. Musacchio E, Valvason C, Botsios C, Ostuni F, Furlan A, Ramonda R, Modesti V, Sartori L, Punzi L (2009) The tumor necrosis factor-{alpha}-blocking agent infliximab inhibits interleukin 1beta (IL-1beta) and IL-6 gene expression in human osteoblastic cells. J Rheumatol 36:1575–1579PubMedCrossRefGoogle Scholar
  139. Mutabaruka MS, Aoulad Aissa M, Delalandre A, Lavigne M, Lajeunesse D (2010) Local leptin production in osteoarthritis subchondral osteoblasts may be responsible for their abnormal phenotypic expression. Arthritis Res Ther 12:R20PubMedCrossRefGoogle Scholar
  140. Nagat T, Bellows CG, Kasugai S, Butler WT, Sodek J (1991) Biosynthesis of bone proteins [SPP-1 (secreted phosphoprotein-1, osteopontin), BSP (bone sialoprotein) and SPARC (osteonectin)] in association with mineralized-tissue formation by fetal-rat calvarial cells in culture. J Biochem 274:513–520Google Scholar
  141. Nakasaki M, Yoshioka K, Miyamoto Y, Sasaki T, Yoshikawa H, Itoh K (2008) IGF-I secreted by osteoblasts acts as a potent chemotactic factor for osteoblasts. Bone 43:869–879PubMedCrossRefGoogle Scholar
  142. Nakayama Y, Mezawa M, Araki S, Sasaki Y, Wang S, Han J, Li X, Takai H, Ogata Y (2009) Nicotine suppresses bone sialoprotein gene expression. J Periodontal Res 44:657–663PubMedCrossRefGoogle Scholar
  143. Neidlinger-Wilke C, Stalla I, Claes L, Brand R, Hoellen I, Rübenacker S, Arand M, Kinzl L (1995) Human osteoblasts from younger normal and osteoporotic donors show differences in proliferation and TGF beta-release in response to cyclic strain. J Biomech 28:1411–1418PubMedCrossRefGoogle Scholar
  144. Ogawa E, Inuzuka M, Maruyama M, Satake M, Naito-Fujimoto M, Ito Y, Shigesada K (1993) Molecular cloning and characterization of PEBP2 beta, the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2 alpha. Virology 194:314–331PubMedCrossRefGoogle Scholar
  145. Oh KW, Rhee EJ, Lee WY, Kim SW, Baek KH, Kang MI, Yun EJ, Park CY, Ihm SH, Choi MG, Yoo HJ, Park SW (2005) Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males. Clin Endocrinol 62:92–98CrossRefGoogle Scholar
  146. Ohnaka K, Taniguchi H, Kawate H, Nawata H, Takayanagi R (2004) Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts: novel mechanism of glucocorticoid-induced osteoporosis. Biochem Biophys Res Commun 318:259–264PubMedCrossRefGoogle Scholar
  147. Oldberg A, Franzen A, Heinegard D (1986) Cloning and sequence analysis of rat bone sialoprotein (osteopontin)cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci USA 83:8819–8823PubMedCrossRefGoogle Scholar
  148. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ (1997) Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765–771PubMedCrossRefGoogle Scholar
  149. Owen M (1988) Marrow stromal stem cells. J Cell Sci Suppl 10:63–76PubMedGoogle Scholar
  150. Owen TA, Aronow M, Shalhoub V, Barone LM, Wilning L, Tassinari MS, Kennedy MB, Pockwinse S, Lian JB, Stein GS (1990) Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. J Cell Physiol 143:420–430PubMedCrossRefGoogle Scholar
  151. Panagakos F, Fernandez C, Kumar S (1996) Ultrastructural analysis of mineralized matrix from human osteoblastic cells: effect of tumor necrosis factor-alpha. Mol Cell Biochem 158:81–89PubMedGoogle Scholar
  152. Pap T, Müller-Ladner U, Gay RE, Gay S (2000) Fibroblast biology. Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis. Arthritis Res 2:361–367PubMedCrossRefGoogle Scholar
  153. Perrini S, Natalicchio A, Laviola L, Cignarelli A, Melchiorre M, De Stefano F, Caccioppoli C, Leonardini A, Martemucci S, Belsanti G, Miccoli S, Ciampolillo A, Corrado A, Cantatore FP, Giorgino R, Giorgino F (2008) Abnormalities of insulin-like growth factor-I signaling and impaired cell proliferation in osteoblasts from subjects with osteoporosis. Endocrinology 149:1302–1313PubMedCrossRefGoogle Scholar
  154. Pettit AR, Ji H, Stechow D von, Müller R, Goldring SR, Choi Y, Benoist C, Gravallese EM (2001) TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol 159:1689–1699PubMedCrossRefGoogle Scholar
  155. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMedCrossRefGoogle Scholar
  156. Radin EL, Rose RM (1986) Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res 213:34–40PubMedGoogle Scholar
  157. Raisz LA (2005) Pathogeneis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115:3318–3325PubMedCrossRefGoogle Scholar
  158. Reseland JE, Syversen U, Bakke I, Qvigstad G, Eide LG, Hjertner O, Gordeladze JO, Drevon CA (2001) Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization. J Bone Miner Res 16:1426–1433PubMedCrossRefGoogle Scholar
  159. Rodríguez JP, Garat S, Gajardo H, Pino AM, Seitz G (1999) Abnormal osteogenesis in osteoporotic patients is reflected by altered mesenchymal stem cells dynamics. J Cell Biochem 75:414–423PubMedCrossRefGoogle Scholar
  160. Rodríguez JP, Astudillo P, Ríos S, Pino AM (2008) Involvement of adipogenic potential of human bone marrow mesenchymal stem cells (MSCs) in osteoporosis. Curr Stem Cell Res Ther 3:208–218PubMedCrossRefGoogle Scholar
  161. Rogers A, Eastell R (2005) Circulating osteoprotegerin and receptor activator for nuclear factor kappaB ligand: clinical utility in metabolic bone disease assessment. J Clin Endocrinol Metab 90:6323–6331PubMedCrossRefGoogle Scholar
  162. Roodman GD (1999) Cell biology of the osteoclast. Exp Hematol 27:1229–1241PubMedCrossRefGoogle Scholar
  163. Ross FP, Chappel J, Alvarez JI, Sander D, Butler WD, Farach-carson MC, Mintz KA, Robey P, Teitelbaum SL, Cheresh DA (1993) Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin αvβ3 potentiate bone resorption. J Biol Chem 268:9901–9907PubMedGoogle Scholar
  164. Rothem DE, Rothem L, Soudry M, Dahan A, Eliakim R (2009) Nicotine modulates bone metabolism-associated gene expression in osteoblast cells. J Bone Miner Metab 27:555–561PubMedCrossRefGoogle Scholar
  165. Shealy DJ, Wooley PH, Emmell E, Volk A, Rosenberg A, Treacy G, Wagner CL, Mayton L, Griswold DE, Song XY (2002) Anti-TNF-alpha antibody allows healing of joint damage in polyarthritic transgenic mice. Arthritis Res 4:R7PubMedCrossRefGoogle Scholar
  166. Silvestris F, Cafforio P, Calvani N, Dammacco F (2004) Impaired osteoblastogenesis in myeloma bone disease: role of upregulated apoptosis by cytokines and malignant plasma cells. Br J Haematol 126:475–486PubMedCrossRefGoogle Scholar
  167. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319PubMedCrossRefGoogle Scholar
  168. Stein GS, Stein JL, Wijnen AJ van, Lian JB (1992) Regulation of histone gene expression. Curr Opin Cell Biol 4:166–173PubMedCrossRefGoogle Scholar
  169. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317PubMedCrossRefGoogle Scholar
  170. Takuwa Y, Ohse C, Wang EA, Wozney JM, Yamashita K (1991) Bone morphogenetic protein-2 stimulates alkaline phosphatase activity and collagen synthesis in cultured osteoblastic cells, MC3T3–E1. Biochem Biophys Res Commun 174:96–101PubMedCrossRefGoogle Scholar
  171. Tamara A (2006) Buried alive: how osteoblasts become osteocytes. Dev Dyn 235:176–190CrossRefGoogle Scholar
  172. Tat SK, Padrines M, Theoleyre S, Couillaud-Battaglia S, Heymann D, Redini F, Fortun Y (2006) OPG/membranous-RANKL complex is internalized via the clathrin pathway before a lysosomal and a proteasomal degradation. Bone 39:706–715PubMedCrossRefGoogle Scholar
  173. Tat SK, Pelletier JP, Lajeunesse D, Fahmi H, Duval N, Martel-Pelletier J (2008) Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: influence of osteotropic factors. Bone 43:284–291PubMedCrossRefGoogle Scholar
  174. Teti A, Grano M, Colucci S, Cantatore FP, Loperfido MC, Zallone AZ (1991) Osteoblast-osteoclast relationships in bone resorption: osteoblasts enhance osteoclast activity in a serum-free co-culture system. Biochem Biophys Res Commun 179:634–640PubMedCrossRefGoogle Scholar
  175. Thomas GP, Baker SU, Eisman JA, Gardiner EM (2001) Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts. J Endocrinol 170:451–460PubMedCrossRefGoogle Scholar
  176. Tian QX, Huang GY, Zhou JL, Liu QH, DU XR (2007) Effects of calcitonin on osteoblast cell proliferation and OPG/RANKL expression: experiment with mouse osteoblasts. Zhonghua Yi Xue Za Zhi 87:1501-1505PubMedGoogle Scholar
  177. Tontonoz P, Hu E, Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79:1147–1156PubMedCrossRefGoogle Scholar
  178. Torricelli P, Fini M, Giavaresi G, Giardino R (2002) Human osteoblast cultures from osteoporotic and healthy bone: biochemical markers and cytokine expression in basal conditions and in response to 1, 25(OH)2D3. Artif Cells Blood Substit Immobil Biotechnol 30:219–227PubMedCrossRefGoogle Scholar
  179. Tsuji K, Ito Y, Noda M (1998) Expression of the PEBP2alphaA/AML3/CBFA1 gene is regulated by BMP4/7 heterodimer and its overexpression suppresses type I collagen and osteocalcin gene expression in osteoblastic and nonosteoblastic mesenchymal cells. Bone 22:87–92PubMedCrossRefGoogle Scholar
  180. Tsurukai T, Udagawa N, Matsuzaki K, Takahashi N, Suda T (2000) Roles of macrophage-colony stimulating factor and osteoclast differentiation factor in osteoclastogenesis. J Bone Miner Metab 18:177–184PubMedCrossRefGoogle Scholar
  181. Utting JC, Robins SP, Brandao-Burch A, Orriss IR, Behar J, Arnett TR (2006) Hypoxia inhibits the growth, differentiation and bone-forming capacity of rat osteoblasts. Exp Cell Res 312:1693–1702PubMedCrossRefGoogle Scholar
  182. Valdes AM, Spector TD (2010) The genetic epidemiology of osteoarthritis. Curr Opin Rheumatol 22:139–143PubMedCrossRefGoogle Scholar
  183. Verma S, Rajaratnam JH, Denton J, Hoyland JA, Byers RJ (2002) Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis. J Clin Pathol 55:693–698PubMedCrossRefGoogle Scholar
  184. Walsh NC, Reinwald S, Manning CA, Condon KW, Iwata K, Burr DB, Gravallese EM (2009) Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis. J Bone Miner Res 24:1572–1585PubMedCrossRefGoogle Scholar
  185. Wang EA, Israel DI, Kelly S, Luxenberg DP (1993) Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. Growth Factors 9:57–71PubMedCrossRefGoogle Scholar
  186. Weintraub H (1993) The MyoD family and myogenesis: redundancy, networks, and thresholds. Cell 75:1241–1244PubMedCrossRefGoogle Scholar
  187. Westendorf JJ, Kahler RA, Schroeder TN (2004) Wnt signaling in osteoblasts and bone diseases. Gene 341:19–39PubMedCrossRefGoogle Scholar
  188. Whitson SW, Harrison W, Dunlap MK, Bowers DE Jr, Fisher LW, Robey PG, Termine JD (1984) Fetal bovine cells synthesize bone specific matrix proteins. J Cell Biol 88:607–614CrossRefGoogle Scholar
  189. Wognum AW, Gils FC van, Wagemaker G (1993) Flow cytometric detection of receptors for interleukin-6 on bone marrow and peripheral blood cells of humans and rhesus monkeys. Blood 81:2036–2043PubMedGoogle Scholar
  190. Yamaguchi A, Katagiri T, Ikeda T, Wozney JM, Rosen V, Wang EA, Kahn AJ, Suda T, Yoshiki S (1991) Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro. J Cell Biol 113:681–687PubMedCrossRefGoogle Scholar
  191. Yamaguchi A, Komori T, Suda T (2000) Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocr Rev 21:393–411PubMedCrossRefGoogle Scholar
  192. Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95:3597–3602PubMedCrossRefGoogle Scholar
  193. Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Suda T, Matsuo K (2006) Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab 4:111–121PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Anna Neve
    • 1
  • Addolorata Corrado
    • 1
  • Francesco Paolo Cantatore
    • 1
    • 2
    Email author
  1. 1.Rheumatology Clinic, Department of Medical and Occupational SciencesUniversity of FoggiaFoggiaItaly
  2. 2.Rheumatology ClinicUniversity of FoggiaFoggiaItaly

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