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Osteoblast ontogeny and implications for bone pathology: an overview

Cell and Tissue Research volume 355, pages 23–33 (2014)Cite this article

Abstract

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.

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References

  • 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 138:5067–5070

    CAS  PubMed  Google Scholar 

  • 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 4:718–746

    Google Scholar 

  • Baghaban Eslaminejad M, Jahangir S, Aghdami N (2011) Mesenchymal stem cells from murine amniotic fluid as a model for preclinical investigation. Arch Iran Med 14:96–103

    PubMed  Google Scholar 

  • 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 23:1203–1214

    CAS  PubMed  Google Scholar 

  • Bieback K, Klüter H (2007) Mesenchymal stromal cells from umbilical cord blood. Curr Stem Cell Res Ther 2:310–323

    CAS  PubMed  Google Scholar 

  • Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, Nikbin B (2006) Aging of mesenchymal stem cell in vitro. BMC Cell Biol 10:7–14

    Google Scholar 

  • Bonewald LF (2007) Osteocytes as dynamic multifunctional cells. Ann N Y Acad Sci 1116:281–290

    CAS  PubMed  Google Scholar 

  • Bonucci E (1992) Role of collagen fibrils in calcification. In: Bonucci E (ed) Calcification in biological systems. CRC Press, Boca Raton, pp 19–41

    Google Scholar 

  • 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 18:933–944

    CAS  PubMed  Google Scholar 

  • 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 145:527–538

    CAS  PubMed  Google Scholar 

  • Byers PH, Steiner RD (1992) Osteogenesis imperfecta. Annu Rev Med 43:269–282

    CAS  PubMed  Google Scholar 

  • Canalis E, McCarthy TL, Centrella M (1989) Growth factors and the skeletal system. J Endocrinol Invest 12:577–584

    CAS  PubMed  Google Scholar 

  • Cui CB, Cooper LF, Yang X, Karsenty G, Aukhiand I (2003) Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ. Mol Cell Biol 23:1004–1013

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 277:816–822

    PubMed  Google Scholar 

  • 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 15:2064–2077

    CAS  PubMed  Google Scholar 

  • 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 13:156–163

    CAS  PubMed  Google Scholar 

  • 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 125:971–986

    CAS  PubMed  Google Scholar 

  • 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 13:1025–1036

    CAS  PubMed  Google Scholar 

  • 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 111:1221–1230

    CAS  PubMed Central  PubMed  Google Scholar 

  • El Miedany YM, Mehanna AN, El Baddini MA (2000) Altered bone mineral metabolism in patients with osteoarthritis. Joint Bone Spine 6:521–527

    Google Scholar 

  • 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 19:1027–1034

    CAS  PubMed  Google Scholar 

  • Frost HMJ (2001) Why should many skeletal scientists and clinicians learn the Utah paradigm of skeletal physiology. J Musculoskelet Neuronal Interact 2:121–130

    CAS  PubMed  Google Scholar 

  • 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 77:45–54

    CAS  PubMed Central  PubMed  Google Scholar 

  • Giachelli CM, Steitz S (2000) Osteopontin: a versatile regulator of inflammation and biomineralization. Matrix Biol 19:615–622

    CAS  PubMed  Google Scholar 

  • Giustina A, Mazziotti G, Canalis E (2008) Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29:535–559

    CAS  PubMed  Google Scholar 

  • 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 179:1594–1600

    CAS  PubMed  Google Scholar 

  • 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 36:1354–1369

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 51:42–61

    CAS  Google Scholar 

  • 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 107:19879–19884

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hauschka PV, Chen TL, Mavrakos AE (1988) Polypeptide growth factors in bone matrix. Ciba Found Symp 136:207–225

    CAS  PubMed  Google Scholar 

  • He Q, Wan C, Li G (2007) Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells 25:69–77

    CAS  PubMed  Google Scholar 

  • 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 41:891–899

    CAS  PubMed  Google Scholar 

  • 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:R100

    PubMed Central  PubMed  Google Scholar 

  • 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 5:262–264

    Google Scholar 

  • 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 286:12328–12339

    CAS  PubMed  Google Scholar 

  • 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 88:792–806

    CAS  PubMed  Google Scholar 

  • Huang J, Zhao L, Xing L, Chen D (2010) MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells 28:357–364

    PubMed Central  PubMed  Google Scholar 

  • 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 106:20794–20799

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jayakumar P, Di Silvio L (2010) Osteoblasts in bone tissue engineering. Proc Inst Mech Eng H 224:1415–1440

    CAS  PubMed  Google Scholar 

  • 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 418:41–49

    CAS  PubMed  Google Scholar 

  • 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 69:450–457

    CAS  PubMed  Google Scholar 

  • Junqueira LC, Carneiro J (2008) Tesutul osos. In: Cuculici GP, Gheorghiu AW (eds) Histologie. Editura Medicala Callisto, Bucharest, pp 134–152

    Google Scholar 

  • 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:e7535

    PubMed Central  PubMed  Google Scholar 

  • 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 143:1594–1601

    CAS  PubMed  Google Scholar 

  • Kapinas K, Delany AM (2011) MicroRNA biogenesis and regulation of bone remodeling. Arthritis Res Ther 13:220–231

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 108:216–224

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 285:25221–25231

    CAS  PubMed  Google Scholar 

  • Karsenty G (2008) Transcriptional control of skeletogenesis. Annu Rev Genomics Hum Genet 9:183–196

    CAS  PubMed  Google Scholar 

  • 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 25:107–108

    CAS  PubMed  Google Scholar 

  • Kartsogiannis V, Ng KW (2004) Cell lines and primary cell cultures in the study of bone cell biology. Mol Cell Endocrinol 228:79–102

    CAS  PubMed  Google Scholar 

  • 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 149:5984–5995

    CAS  PubMed  Google Scholar 

  • 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 211:253–260

    CAS  PubMed  Google Scholar 

  • 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 24:816–825

    CAS  PubMed  Google Scholar 

  • Kogianni G, Noble BS (2007) The biology of osteocytes. Curr Osteoporos Rep 5:81–86

    PubMed  Google Scholar 

  • Komori T (2006) Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 99:1233–1239

    CAS  PubMed  Google Scholar 

  • 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 89:755–764

    CAS  PubMed  Google Scholar 

  • 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 19:614–622

    PubMed  Google Scholar 

  • 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 106:59–66

    CAS  PubMed  Google Scholar 

  • Krampera M, Pizzolo G, Aprili G, Franchini M (2006a) Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone 39:678–683

    CAS  PubMed  Google Scholar 

  • 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 24:386–398

    CAS  PubMed  Google Scholar 

  • Lajeunesse D, Reboul P (2003) Subchondral bone in osteoarthritis: a biologic link with articular cartilage leading to abnormal remodeling. Curr Opin Rheumatol 15:628–633

    PubMed  Google Scholar 

  • 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 105:13906–13911

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 119:3666–3677

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 284:15676–15684

    CAS  PubMed  Google Scholar 

  • 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 14:1–41

    CAS  PubMed  Google Scholar 

  • 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 8:212–227

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 25:807–815

    PubMed  Google Scholar 

  • 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 155:157–166

    CAS  PubMed  Google Scholar 

  • 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 23:287–295

    CAS  PubMed  Google Scholar 

  • 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–S49

    CAS  PubMed  Google Scholar 

  • Martin RB, Burr D, Sharkey N (1998) Skeletal biology. In: Martin RB (ed) Skeletal tissue mechanics. Springer, New York, pp 29–77

    Google Scholar 

  • 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 29:667–672

    CAS  PubMed  Google Scholar 

  • 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 236:1876–1890

    CAS  PubMed  Google Scholar 

  • 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 62:1733–1743

    CAS  PubMed  Google Scholar 

  • Miller SC, de Saint-Georges L, Bowman BM, Jee WS (1989) Bone lining cells: structure and function. Scanning Microsc 3:953–960

    CAS  PubMed  Google Scholar 

  • 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 368:267–272

    CAS  PubMed  Google Scholar 

  • 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 583:2263–2268

    CAS  PubMed  Google Scholar 

  • Nakamura H (2007) Morphology, functions, and differentiation of bone cells. J Hard Tissue Biol 16:15–22

    CAS  Google Scholar 

  • Nakashima K, De Crombrugghe B (2003) Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet 19:458–466

    CAS  PubMed  Google Scholar 

  • 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 108:17–29

    CAS  PubMed  Google Scholar 

  • Neve A, Corrado A, Cantatore FP (2011) Osteoblast physiology in normal and pathological conditions. Cell Tissue Res 343:289–302

    CAS  PubMed  Google Scholar 

  • 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 978-85-89109-06-2.1

  • Oreffo ROC, Cooper C, Mason C, Clements M (2005) Mesenchymal stem cells lineage, plasticity, and skeletal therapeutic potential. Stem Cell Rev 1:169–178

    CAS  PubMed  Google Scholar 

  • 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 6:15–27

    CAS  PubMed  Google Scholar 

  • 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 5:1689–1699

    Google Scholar 

  • 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 284:143–147

    CAS  PubMed  Google Scholar 

  • Raisz LA (2005) Pathogenesis of osteoporosis: concepts, conflicts and prospects. J Clin Invest 115:3318–3325

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 13:763–773

    CAS  PubMed  Google Scholar 

  • Robey PG, Young MF, Fisher LW, McClain TD (1989) Thrombospondin is an osteoblast derived component of mineralized extracellular matrix. J Cell Biol 108:719–727

    CAS  PubMed  Google Scholar 

  • Robling AG, Castillo AB, Turner CH (2006) Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng 8:455–498

    CAS  PubMed  Google Scholar 

  • Rodan GA (1992) Introduction to bone biology. Bone 13:S3–S6

    CAS  PubMed  Google Scholar 

  • Rowe DW (2008) Osteogenesis imperfecta. In: Bilezikian JP, Raisz LG, Martin TJ (eds) Principles of bone biology, vol 1. Academic Press, New York, pp 1511–1532

    Google Scholar 

  • 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 131:324–336

    CAS  PubMed  Google Scholar 

  • 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) 66:487–492

    Google Scholar 

  • 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 168:899–910

    CAS  PubMed  Google Scholar 

  • 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:e5605

    PubMed Central  PubMed  Google Scholar 

  • 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 93:339–346

    PubMed  Google Scholar 

  • 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:R7

    PubMed Central  PubMed  Google Scholar 

  • Sillence DO, Senn A, Danks DM (1979) Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 16:101–116

    CAS  PubMed  Google Scholar 

  • 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 30:18–25

    CAS  PubMed  Google Scholar 

  • 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 22:823–831

    PubMed  Google Scholar 

  • 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 67:66–70

    CAS  PubMed  Google Scholar 

  • Sommerfeldt DW, Rubin CT (2001) Biology of bone and how it orchestrates the form and function of the skeleton. Eur Spine J 10:S86–S95

    PubMed Central  PubMed  Google Scholar 

  • 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 20:345–357

    CAS  PubMed  Google Scholar 

  • 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 166:359–371

    PubMed  Google Scholar 

  • 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 26:295–304

    Google Scholar 

  • 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 43:284–291

    CAS  PubMed  Google Scholar 

  • 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 18:985–995

    CAS  PubMed  Google Scholar 

  • 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 132:563–574

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 36:243–253

    CAS  PubMed  Google Scholar 

  • Vimalraj S, Selvamurugan N (2012) MicroRNAs: synthesis, gene regulation and osteoblast differentiation. Curr Issues Mol Biol 15:7–18

    CAS  PubMed  Google Scholar 

  • 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 9:1572–1585

    Google Scholar 

  • Wang T, Xu Z (2010) miR-27 promotes osteoblast differentiation by modulating Wnt signaling. Biochem Biophys Res Commun 402:186–189

    CAS  PubMed  Google Scholar 

  • 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 16:1388–1398

    CAS  PubMed  Google Scholar 

  • 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 24:1889–1904

    CAS  PubMed  Google Scholar 

  • 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 22:3955–3961

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 8:1–10

    Google Scholar 

  • 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 108:9863–9868

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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 103:19004–19009

    CAS  PubMed Central  PubMed  Google Scholar 

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Affiliations

  1. Regenerative Medicine Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, Romania

    Irina Titorencu, Vasile Pruna & Victor V. Jinga

  2. Cellular and Molecular Biology Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, Bucharest, Romania

    Maya Simionescu

Authors
  1. Irina Titorencu
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  2. Vasile Pruna
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  3. Victor V. Jinga
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  4. Maya Simionescu
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Corresponding author

Correspondence to Maya Simionescu.

Additional information

The authors gratefully acknowledge the financial support of the Romanian National CNCSIS (grant IDEI PCCE code 248/2010) and the Romanian Academy.

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Titorencu, I., Pruna, V., Jinga, V.V. et al. Osteoblast ontogeny and implications for bone pathology: an overview. Cell Tissue Res 355, 23–33 (2014). https://doi.org/10.1007/s00441-013-1750-3

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  • DOI: https://doi.org/10.1007/s00441-013-1750-3

Keywords

  • Osteoblasts
  • Bone
  • Osteoblasts ontogeny
  • Mesenchymal stem cell
  • Bone pathology