Cell and Tissue Research

, Volume 355, Issue 1, pp 23–33 | Cite as

Osteoblast ontogeny and implications for bone pathology: an overview

  • Irina Titorencu
  • Vasile Pruna
  • Victor V. Jinga
  • Maya Simionescu


Osteoblasts are specialized mesenchyme-derived cells accountable for bone synthesis, remodelling and healing. Differentiation of osteoblasts from mesenchymal stem cells (MSC) towards osteocytes is a multi-step process strictly controlled by various genes, transcription factors and signalling proteins. The aim of this review is to provide an update on the nature of bone-forming osteoblastic cells, highlighting recent data on MSC—osteoblast—osteocyte transformation from a molecular perspective and to discuss osteoblast malfunctions in various bone diseases. We present here the consecutive stages occurring in the differentiation of osteoblasts from MSC, the transcription factors involved and the role of miRNAs in the process. Recent data concerning the pathogenic mechanisms underlying the loss of bone mass and architecture caused by malfunctions in the synthetic activity and metabolism of osteoblasts in osteoporosis, osteogenesis imperfecta, osteoarthritis and rheumatoid arthritis are discussed. The newly acquired knowledge of the ontogeny of osteoblasts will assist in unravelling the abnormalities taking place during their differentiation and will facilitate the prevention and/or treatment of bone diseases by therapy directed against altered molecules and mechanisms.


Osteoblasts Bone Osteoblasts ontogeny Mesenchymal stem cell Bone pathology 


  1. Arts J, Kuiper GGJM, Janssen JMMF, Gustafsson J-A, Lowik CWGM, Pols HAP, Van Leeuwen JPTM (1997) Differential expression of estrogen receptors a and b during differentiation of human osteoblast SV-HFO cells. Endocrinology 138:5067–5070PubMedGoogle Scholar
  2. Arvidson K, Abdallah BM, Applegate LA, Baldini N, Cenni E, Gomez-Barrena E, Granch D, Kassem M, Konttinen YT, Mustafa K, Pioletti DP, Sillat T, Finne-Wistrand A (2011) Bone regeneration and stem cells. J Cell Mol Med 4:718–746Google Scholar
  3. Baghaban Eslaminejad M, Jahangir S, Aghdami N (2011) Mesenchymal stem cells from murine amniotic fluid as a model for preclinical investigation. Arch Iran Med 14:96–103PubMedGoogle Scholar
  4. Baniwal SK, Khalid O, Sir D, Buchanan G, Coetzee GA, Frenkelb B (2009) Repression of Runx-2 by androgen receptor (AR) in osteoblasts and prostate cancer cells: AR binds Runx-2 and abrogates its recruitment to DNA. Mol Endocrinol 23:1203–1214PubMedGoogle Scholar
  5. Bieback K, Klüter H (2007) Mesenchymal stromal cells from umbilical cord blood. Curr Stem Cell Res Ther 2:310–323PubMedGoogle Scholar
  6. Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, Nikbin B (2006) Aging of mesenchymal stem cell in vitro. BMC Cell Biol 10:7–14Google Scholar
  7. Bonewald LF (2007) Osteocytes as dynamic multifunctional cells. Ann N Y Acad Sci 1116:281–290PubMedGoogle Scholar
  8. Bonucci E (1992) Role of collagen fibrils in calcification. In: Bonucci E (ed) Calcification in biological systems. CRC Press, Boca Raton, pp 19–41Google Scholar
  9. Bosch P, Musgrave DS, Lee JY, Cummins J, Shuler T, Ghivizzani TC, Evans T, Robbins TD, Huard J (2000) Osteoprogenitor cells within skeletal muscle. J Orthop Res 18:933–944PubMedGoogle Scholar
  10. Burgess TL, Qian Y, Kaufman S, Ring BD, Van G, Capparelli C, Kelley M, Hsu H, Boyle WJ, Dunstan CR, Hu S, Lacey DLJ (1999) The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol 145:527–538PubMedGoogle Scholar
  11. Byers PH, Steiner RD (1992) Osteogenesis imperfecta. Annu Rev Med 43:269–282PubMedGoogle Scholar
  12. Canalis E, McCarthy TL, Centrella M (1989) Growth factors and the skeletal system. J Endocrinol Invest 12:577–584PubMedGoogle Scholar
  13. Cui CB, Cooper LF, Yang X, Karsenty G, Aukhiand I (2003) Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ. Mol Cell Biol 23:1004–1013PubMedCentralPubMedGoogle Scholar
  14. D’Alonzo RC, Selvamurugan N, Karsenty G, Partridge NC (2002) Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation. J Biol Chem 277:816–822PubMedGoogle Scholar
  15. Denger S, Reid G, Kos M, Flouriot G, Parsch D, Brand H, Korach KS, Sonntag-Buck V, Gannon F (2001) ER α gene expression in human primary osteoblasts: evidence for the expression of two receptor proteins. Mol Endocrinol 15:2064–2077PubMedGoogle Scholar
  16. Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, Korb A, Smolen J, Hoffmann M, Scheinecker C, van der Heide D, Landewe R, Lacey D, Richards WG, Schett G (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156–163PubMedGoogle Scholar
  17. Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Farinas I, Karsenty G, Grosschedl R (2006) SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell 125:971–986PubMedGoogle Scholar
  18. Ducy P, Starbuck M, Priemel M, Shen J, Pinero G, Geoffroy V, Amling M, Karsenty G (1999) A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev 13:1025–1036PubMedGoogle Scholar
  19. Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL (2003) Role of RANK ligand in mediating increased bone resorbtion in early postmenopausal women. J Clin Invest 111:1221–1230PubMedCentralPubMedGoogle Scholar
  20. El Miedany YM, Mehanna AN, El Baddini MA (2000) Altered bone mineral metabolism in patients with osteoarthritis. Joint Bone Spine 6:521–527Google Scholar
  21. Eppell SJ, Tong W, Katz JL, Kuhn L, Glimcher MJ (2001) Shape and size of isolated bone mineralites measured using atomic force microscopy. J Orthop Res 19:1027–1034PubMedGoogle Scholar
  22. Frost HMJ (2001) Why should many skeletal scientists and clinicians learn the Utah paradigm of skeletal physiology. J Musculoskelet Neuronal Interact 2:121–130PubMedGoogle Scholar
  23. Gericke A, Qin C, Spevak L, Fujimoto Y, Butler WT, Sorensen ES, Boskey AL (2005) Importance of phosphorylation for osteopontin regulation of biomineralization. Calcif Tissue Int 77:45–54PubMedCentralPubMedGoogle Scholar
  24. Giachelli CM, Steitz S (2000) Osteopontin: a versatile regulator of inflammation and biomineralization. Matrix Biol 19:615–622PubMedGoogle Scholar
  25. Giustina A, Mazziotti G, Canalis E (2008) Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29:535–559PubMedGoogle Scholar
  26. Goettsch C, Rauner M, Pacyna N, Hempel U, Bornstein SR, Hofbauer LC (2011) miR-125b regulates calcification of vascular smooth muscle cells. Am J Pathol 179:1594–1600PubMedGoogle Scholar
  27. Goff LA, Boucher S, Ricupero CL, Fenstermacher S, Swerdel M, Chase LG, Adams CC, Chesnut J, Lakshmipathy U, Hart RP (2008) Differentiating human multipotent mesenchymal stromal cells regulate microRNAs: prediction of microRNA regulation by PDGF during osteogenesis. Exp Hematol 36:1354–1369PubMedCentralPubMedGoogle Scholar
  28. Gordeladze JO, Reseland JE, Duroux-Richard I, Apparailly F, Jorgensen C (2010) From stem cells to bone: phenotype acquisition, stabilization, and tissue engineering in animal models. ILAR J 51:42–61Google Scholar
  29. Hassan MQ, Gordon JAR, Belot MM, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2010) A network connecting Runx2, SATB2, and the miR-23a 27a 24–2 cluster regulates the osteoblast differentiation program. Proc Natl Acad Sci U S A 107:19879–19884PubMedCentralPubMedGoogle Scholar
  30. Hauschka PV, Chen TL, Mavrakos AE (1988) Polypeptide growth factors in bone matrix. Ciba Found Symp 136:207–225PubMedGoogle Scholar
  31. He Q, Wan C, Li G (2007) Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells 25:69–77PubMedGoogle Scholar
  32. 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. Arthritis Rheum 41:891–899PubMedGoogle Scholar
  33. 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-β/bone morphogenic protein signaling. Arthritis Res Ther 9:R100PubMedCentralPubMedGoogle Scholar
  34. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE, Brenner MK (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:262–264Google Scholar
  35. Hu R, Liu W, Li H, Yang L, Chen C, Xia ZY, Guo LJ, Xie H, Zhou HD, Wu XP, Luo XH (2011) A Runx2/miR-3960/miR-2861 regulatory feedback loop during mouse osteoblast differentiation. J Biol Chem 286:12328–12339PubMedGoogle Scholar
  36. Huang GTJ, Gronthos S, Shi S (2009) Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 88:792–806PubMedGoogle Scholar
  37. Huang J, Zhao L, Xing L, Chen D (2010) MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells 28:357–364PubMedCentralPubMedGoogle Scholar
  38. Inose H, Ochi H, Kimura A, Fujita K, Xu R, Sato S, Iwasaki M, Sunamura S, Takeuchi Y, Fukumoto S, Saito K, Nakamura T, Siomi H, Ito H, Arai Y, Shinomiya K, Takeda S (2009) A microRNA regulatory mechanism of osteoblast differentiation. Proc Natl Acad Sci U S A 106:20794–20799PubMedCentralPubMedGoogle Scholar
  39. Jayakumar P, Di Silvio L (2010) Osteoblasts in bone tissue engineering. Proc Inst Mech Eng H 224:1415–1440PubMedGoogle Scholar
  40. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49PubMedGoogle Scholar
  41. Jones E, Churchman SM, English A, Buch MH, Horner EA, Burgoyne CH, Reece R, Kinsey S, Emery P, McGonagle D, Ponchel F (2010) Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level. Ann Rheum Dis 69:450–457PubMedGoogle Scholar
  42. Junqueira LC, Carneiro J (2008) Tesutul osos. In: Cuculici GP, Gheorghiu AW (eds) Histologie. Editura Medicala Callisto, Bucharest, pp 134–152Google Scholar
  43. Kahai S, Lee SC, Lee DY, Yang J, Li M, Wang CH, Jiang Z, Zhang Y, Peng C, Yang BB (2009) MicroRNA miR-378 regulates nephronectin expression modulating osteoblast differentiation by targeting GalNT-7. PLoS One 4:e7535PubMedCentralPubMedGoogle Scholar
  44. Kalajzic I, Terzic J, Rumboldt Z, Mack K, Naprta A, Ledgard F, Gronowicz G, Clark SH, Rowe DW (2002) Osteoblastic response to the defective matrix in the osteogenesis imperfecta murine (OIM) mouse. Endocrinology 143:1594–1601PubMedGoogle Scholar
  45. Kapinas K, Delany AM (2011) MicroRNA biogenesis and regulation of bone remodeling. Arthritis Res Ther 13:220–231PubMedCentralPubMedGoogle Scholar
  46. Kapinas K, Kessler CB, Delany AM (2009) miR-29 suppression of osteonectin in osteoblasts: regulation during differentiation and by canonical Wnt signalling. J Cell Biochem 108:216–224PubMedCentralPubMedGoogle Scholar
  47. Kapinas K, Kessler C, Ricks T, Gronowicz G, Delany AM (2010) miR-29 modulates Wnt signaling in human osteoblasts through a positive feedback loop. J Biol Chem 285:25221–25231PubMedGoogle Scholar
  48. Karsenty G (2008) Transcriptional control of skeletogenesis. Annu Rev Genomics Hum Genet 9:183–196PubMedGoogle Scholar
  49. Karsenty G, Ducy P, Starbuck M, Priemel M, Shen J, Geoffroy V, Amling M (1999) Cbfa1 as a regulator of osteoblast differentiation and function. Bone 25:107–108PubMedGoogle Scholar
  50. Kartsogiannis V, Ng KW (2004) Cell lines and primary cell cultures in the study of bone cell biology. Mol Cell Endocrinol 228:79–102PubMedGoogle Scholar
  51. Khalid O, Baniwal SK, Purcell DJ, Leclerc N, Gabet Y, Stallcup MR, Coetzee GA, Frenkel B (2008) Modulation of Runx-2 activity by estrogen receptor α: implication for osteoporosis and breast cancer. Endocrinology 149:5984–5995PubMedGoogle Scholar
  52. Kim YJ, Kim BG, Lee SJ, Lee HK, Lee SH, Ryoo HM, Cho JY (2007) The suppressive effect of myeloid Elf-1-like factor (MEF) in osteogenic differentiation. J Cell Physiol 211:253–260PubMedGoogle Scholar
  53. Kim YJ, Bae SW, Yu SS, Bae YC, Jung JS (2009) miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue. J Bone Miner Res 24:816–825PubMedGoogle Scholar
  54. Kogianni G, Noble BS (2007) The biology of osteocytes. Curr Osteoporos Rep 5:81–86PubMedGoogle Scholar
  55. Komori T (2006) Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 99:1233–1239PubMedGoogle Scholar
  56. 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 89:755–764PubMedGoogle Scholar
  57. Kozloff KM, Carden A, Bergwitz C, Forlino A, Uveges TE, Morris MD, Marini JC, Goldstein SA (2004) Brittle IV mouse model for osteogenesis imperfecta IV demonstrates postpubertal adaptations to improve whole bone strength. J Bone Miner Res 19:614–622PubMedGoogle Scholar
  58. Krampera M, Pasini A, Rigo A, Scupoli MT, Tecchio C, Malpeli G, Scarpa A, Dazzi F, Pizzolo G, Vinante F (2005) HB-EGF/HER-1 signalling in bone marrow mesenchymal stem cells: inducing cell expansion and reversibly preventing multi-lineage differentiation. Blood 106:59–66PubMedGoogle Scholar
  59. Krampera M, Pizzolo G, Aprili G, Franchini M (2006a) Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone 39:678–683PubMedGoogle Scholar
  60. Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, Santarlasci V, Mazzinghi B, Pizzolo G, Vinante F, Romagnani P, Maggi E, Romagnani S, Annunziato F (2006b) Role of the IFN-γ in the immunomodulatory activity of human mesenchymal stem cells. Stem Cells 24:386–398PubMedGoogle Scholar
  61. Lajeunesse D, Reboul P (2003) Subchondral bone in osteoarthritis: a biologic link with articular cartilage leading to abnormal remodeling. Curr Opin Rheumatol 15:628–633PubMedGoogle Scholar
  62. Li Z, Hassan MQ, Volinia S, van Wijnen AJ, Stein JL, Croce CM, Lian JB, Stein GS (2008) A microRNA signature for a BMP2-induced osteoblast lineage commitment program. Proc Natl Acad Sci U S A 105:13906–13911PubMedCentralPubMedGoogle Scholar
  63. Li H, Xie H, Liu W, Huang B, Tan YF, Liao EY, Xu K, Sheng ZF, Zhou HD, Wu XP, Luo XH (2009a) A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J Clin Invest 119:3666–3677PubMedCentralPubMedGoogle Scholar
  64. Li Z, Hassan MQ, Jafferji M, Aqeilan RI, Garzon R, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2009b) Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem 284:15676–15684PubMedGoogle Scholar
  65. Lian JB, Javed A, Zaidi SK, Lengner C, Montecino M, van Wijnen AJ, Stein JL, Stein GS (2004) Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. Crit Rev Eukaryot Gene Expr 14:1–41PubMedGoogle Scholar
  66. Lian JB, Stein GS, van Wijnen AJ, Stein JL, Hassan MQ, Gaur T, Zhang Y (2012) MicroRNA control of bone formation and homeostasis. Nat Rev Endocrinol 8:212–227PubMedCentralPubMedGoogle Scholar
  67. Lin CS, Xin ZC, Deng CH, Ning H, Lin G, Lue TF (2010) Defining adipose tissue-derived stem cells in tissue and in culture. Histol Histopathol 25:807–815PubMedGoogle Scholar
  68. Liu W, Toyosawa S, Furuichi T, Kanatani N, Yoshida C, Liu Y, Himeno M, Narai S, Yamaguchi A, Komori T (2001) Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J Cell Biol 155:157–166PubMedGoogle Scholar
  69. Luzi E, Marini F, Sala SC, Tognarini I, Galli G, Brandi ML (2008) Osteogenic differentiation of human adipose tissue-derived stem cells is modulated by the miR-26a targeting of the SMAD1 transcription factor. J Bone Miner Res 23:287–295PubMedGoogle Scholar
  70. Manolagas SC, Kousteni S, Chen JR, Schuller M, Plotkin L, Bellido T (2004) Kinase-mediated transcription, activators of nongenotropic estrogen-like signaling (ANGELS), and osteoporosis: a different perspective on the HRT dilemma. Kidney Int Suppl 91:S41–S49PubMedGoogle Scholar
  71. Martin RB, Burr D, Sharkey N (1998) Skeletal biology. In: Martin RB (ed) Skeletal tissue mechanics. Springer, New York, pp 29–77Google Scholar
  72. Maruotti N, Corrado A, Grano M, Colucci S, Cantatore FP (2009) Normal and osteoporotic human osteoblast behaviour after 1,25-dihydroxy-vitamin (D3) stimulation. Rheumatol Int 29:667–672PubMedGoogle Scholar
  73. Maruyama Z, Yoshida CA, Furuichi T, Amizuka N, Ito M, Fukuyama R, Miyazaki T, Kitaura H, Nakamura K, Fujita T, Kanatani N, Moriishi T, Yamana K, Liu W, Kawaguchi H, Nakamura K, Komori T (2007) Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency. Dev Dyn 236:1876–1890PubMedGoogle Scholar
  74. Maurer B, Stanczyk J, Jüngel A, Akhmetshina A, Trenkmann M, Brock M, Kowal-Bielecka O, Gay RE, Michel BA, Distler JH, Gay S, Distler O (2010) MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum 62:1733–1743PubMedGoogle Scholar
  75. Miller SC, de Saint-Georges L, Bowman BM, Jee WS (1989) Bone lining cells: structure and function. Scanning Microsc 3:953–960PubMedGoogle Scholar
  76. Mizuno Y, Yagi K, Tokuzawa Y, Kanesaki-Yatsuka Y, Suda T, Katagiri T, Fukuda T, Maruyama M, Okuda A, Amemiya T, Kondoh Y, Tashiro H, Okazaki Y (2008) miR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation. Biochem Biophys Res Commun 368:267–272PubMedGoogle Scholar
  77. Mizuno Y, Tokuzawa Y, Ninomiya Y, Yagi K, Yatsuka-Kanesaki Y, Suda T, Fukuda T, Katagiri T, Kondoh Y, Amemiya T, Tashiro H, Okazaki Y (2009) miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS Lett 583:2263–2268PubMedGoogle Scholar
  78. Nakamura H (2007) Morphology, functions, and differentiation of bone cells. J Hard Tissue Biol 16:15–22Google Scholar
  79. Nakashima K, De Crombrugghe B (2003) Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet 19:458–466PubMedGoogle Scholar
  80. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, De Crombrugghe B (2002) The novel zinc finger-containing transcription factor Osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29PubMedGoogle Scholar
  81. Neve A, Corrado A, Cantatore FP (2011) Osteoblast physiology in normal and pathological conditions. Cell Tissue Res 343:289–302PubMedGoogle Scholar
  82. Octacílio-Silva S, Marques MM, Evangelista AF, Magalhaes DA, Dernowsek JA, Bombonato-Prado KF, Passos GAS (2010) Defining mRNA targets of microRNAs during osteoblastic differentiation of human mesenchymal stem cells by microarray transcriptional interaction networks. Resumos do 56º Congresso Brasileiro de Genética, ISBN 978-85-89109-06-2.1Google Scholar
  83. Oreffo ROC, Cooper C, Mason C, Clements M (2005) Mesenchymal stem cells lineage, plasticity, and skeletal therapeutic potential. Stem Cell Rev 1:169–178PubMedGoogle Scholar
  84. Partridge NC, Walling HW, Bloch SR, Omura TH, Chan PT, Pearman AT, Chou WY (1996) The regulation and regulatory role of collagenase in bone. Crit Rev Eukaryot Gene Expr 6:15–27PubMedGoogle Scholar
  85. Pettit AR, Ji H, Stechow D, 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 5:1689–1699Google Scholar
  86. 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 284:143–147PubMedGoogle Scholar
  87. Raisz LA (2005) Pathogenesis of osteoporosis: concepts, conflicts and prospects. J Clin Invest 115:3318–3325PubMedCentralPubMedGoogle Scholar
  88. Riggs BL, Khosla S, Melton LJ (1998) A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 13:763–773PubMedGoogle Scholar
  89. Robey PG, Young MF, Fisher LW, McClain TD (1989) Thrombospondin is an osteoblast derived component of mineralized extracellular matrix. J Cell Biol 108:719–727PubMedGoogle Scholar
  90. Robling AG, Castillo AB, Turner CH (2006) Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng 8:455–498PubMedGoogle Scholar
  91. Rodan GA (1992) Introduction to bone biology. Bone 13:S3–S6PubMedGoogle Scholar
  92. Rowe DW (2008) Osteogenesis imperfecta. In: Bilezikian JP, Raisz LG, Martin TJ (eds) Principles of bone biology, vol 1. Academic Press, New York, pp 1511–1532Google Scholar
  93. Sacchetti B, Funari A, Michienzi S, Di CS, Piersanti S, Saggio I, Tagliafico E, Ferrari S, Robey PG, Riminucci M, Bianco P (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336PubMedGoogle Scholar
  94. Sampaio de Mara C, Sartori AR, Duarte AS, Andrade ALL, Pedro AMC, Coimbra IB (2011) Periosteum as a source of mesenchymal stem cells: the effects of TGF-b3 on chondrogenesis. Clinics (Sao Paulo) 66:487–492Google Scholar
  95. Schmidt K, Schinke T, Haberland M, Priemel M, Schilling AF, Mueldner C, Rueger JM, Sock E, Wegner M, Amling M (2005) The high mobility group transcription factor SOX 8 is a negative regulator of osteoblast differentiation. J Cell Biol 168:899–910PubMedGoogle Scholar
  96. Schoolmeesters A, Eklund T, Leake D, Vermeulen A, Smith Q, Aldred SF, Fedorov Y (2009) Functional profiling reveals critical role for miRNA in differentiation of human mesenchymal stem cells. PLoS One 4:e5605PubMedCentralPubMedGoogle Scholar
  97. Sessarego N, Parodi A, Podesta M, Benvenuto F, Mogni M, Raviolo V, Lituania M, Kunkl A, Ferlazzo G, Bricarelli FD, Uccelli A, Frassoni F (2008) Multipotent mesenchymal stromal cells from amniotic fluid: solid perspectives for clinical application. Haematologica 93:339–346PubMedGoogle Scholar
  98. 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:R7PubMedCentralPubMedGoogle Scholar
  99. Sillence DO, Senn A, Danks DM (1979) Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 16:101–116PubMedGoogle Scholar
  100. Sims NA, Dupont S, Krust A, Clement-Lacroix P, Minet D, Resche-Rigon M, Gaillard-Kelly M, Baron R (2002) Deletion of estrogen receptor reveals a regulatory role for estrogen receptors–beta in bone remodeling in females but not in males. Bone 30:18–25PubMedGoogle Scholar
  101. Smith JR, Pochampally R, Perry A, Hsu SC, Prockop DJ (2004) Isolation of a highly clonogenic and multipotential subfraction of adult stem cells from bone marrow stroma. Stem Cells 22:823–831PubMedGoogle Scholar
  102. Somerman MJ, Archer SY, Imm GR, Foster RA (1988) A comparative study of human periodontal ligament cells and gingival fibroblasts in vitro. J Dent Res 67:66–70PubMedGoogle Scholar
  103. Sommerfeldt DW, Rubin CT (2001) Biology of bone and how it orchestrates the form and function of the skeleton. Eur Spine J 10:S86–S95PubMedCentralPubMedGoogle Scholar
  104. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin JT (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20:345–357PubMedGoogle Scholar
  105. Taipaleenmäki H, Bjerre Hokland L, Chen L, Kauppinen S, Kassem M (2012) Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation. Eur J Endocrinol 166:359–371PubMedGoogle Scholar
  106. Tat SK, Pelletier JP, Lajeunesse D, Fahmi H, Lavigne M, Martel-Pelletier J (2008a) 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 26:295–304Google Scholar
  107. Tat SK, Pelletier JP, Lajeunesse D, Fahmi H, Duval N, Martel-Pelletier J (2008b) Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: influence of osteotropic factors. Bone 43:284–291PubMedGoogle Scholar
  108. Tome M, López-Romero P, Albo C, Sepúlveda JC, Fernández-Gutiérrez B, Dopazo A, Bernad A, González MA (2011) MiR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ 18:985–995PubMedGoogle Scholar
  109. Vaculik C, Schuster C, Bauer W, Iram N, Pfisterer K, Kramer G, Reinisch A, Strunk D, Elbe-Bürger A (2012) Human dermis harbors distinct mesenchymal stromal cell subsets. J Invest Dermatol 132:563–574PubMedCentralPubMedGoogle Scholar
  110. Varanasi SS, Datta HK (2005) Characterisation of cytosolic FK506 binding protein 12 and its role in modulating expression of Cbfa1 and Osterix in ROS 17/2.8 cells. Bone 36:243–253PubMedGoogle Scholar
  111. Vimalraj S, Selvamurugan N (2012) MicroRNAs: synthesis, gene regulation and osteoblast differentiation. Curr Issues Mol Biol 15:7–18PubMedGoogle Scholar
  112. Walsh NC, Reinwald S, Manning CA, Keith CKW, Iwata K, Burr DB, Gravallese EM (2009) Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis. J Bone Miner Res 9:1572–1585Google Scholar
  113. Wang T, Xu Z (2010) miR-27 promotes osteoblast differentiation by modulating Wnt signaling. Biochem Biophys Res Commun 402:186–189PubMedGoogle Scholar
  114. Windahl SH, Hollberg K, Vidal O, Gustafsson JA, Ohlsson C, Andersson G (2001) Female estrogen receptor B−/− mice are partially protected against age-related trabecular bone loss. J Bone Miner Res 16:1388–1398PubMedGoogle Scholar
  115. Zhang S, Xiao Z, Luo J, He N, Mahlios J, Quarles LD (2009) Dose-dependent effects of Runx2 on bone development. J Bone Miner Res 24:1889–1904PubMedGoogle Scholar
  116. Zhang JF, Fu WM, He ML, Wang H, Wang WM, Yu SC, Bian XW, Zhou J, Lin MC, Lu G, Poon WS, Kung HF (2011a) MiR-637 maintains the balance between adipocytes and osteoblasts by directly targeting Osterix. Mol Biol Cell 22:3955–3961PubMedCentralPubMedGoogle Scholar
  117. Zhang JF, Fu WM, He ML, Xie WD, Lv Q, Wan G, Li G, Wang H, Lu G, Hu X, Jiang S, Li JN, Lin MCM, Zhang YO, Kung H (2011b) MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling. RNA Biol 8:1–10Google Scholar
  118. Zhang Y, Xie RL, Croce CM, Stein JL, Lian JB, van Wijnen AJ, Stein GS (2011c) A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2. Proc Natl Acad Sci U S A 108:9863–9868PubMedCentralPubMedGoogle Scholar
  119. Zhou G, Zheng Q, Engin F, Munivez E, Chen Y, Sebald E, Krakow D, Lee B (2006) Dominance of SOX 9 function over Runx 2 during skeletogenesis. Proc Natl Acad Sci U S A 103:19004–19009PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Irina Titorencu
    • 1
  • Vasile Pruna
    • 1
  • Victor V. Jinga
    • 1
  • Maya Simionescu
    • 2
  1. 1.Regenerative Medicine DepartmentInstitute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian AcademyBucharestRomania
  2. 2.Cellular and Molecular Biology DepartmentInstitute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian AcademyBucharestRomania

Personalised recommendations