Building Strong Bones: Molecular Regulation of the Osteoblast Lineage

Overview

Journal Nat Rev Mol Cell Biol

Specialties Cell Biology
Molecular Biology

Date 2011 Dec 23

PMID 22189423

Citations 506

Authors

Fanxin Long

Affiliations

Soon will be listed here.

Abstract

The past 15 years have witnessed tremendous progress in the molecular understanding of osteoblasts, the main bone-forming cells in the vertebrate skeleton. In particular, all of the major developmental signals (including WNT and Notch signalling), along with an increasing number of transcription factors (such as RUNX2 and osterix), have been shown to regulate the differentiation and/or function of osteoblasts. As evidence indicates that osteoblasts may also regulate the behaviour of other cell types, a clear understanding of the molecular identity and regulation of osteoblasts is important beyond the field of bone biology.

Citing Articles

miR-138-5p inhibits healing of femoral fracture osteogenesis in rats by modulating osteoblast differentiation via SIRT1/FOXO1 axis.

Dai G, Jiang W, Feng B, Zhang L J Orthop Surg Res. 2025; 20(1):280.

PMID: 40082921 PMC: 11907804. DOI: 10.1186/s13018-025-05667-6.

Unveiling two distinct osteolineage cell populations linked to age-related osteoporosis in adult mice through integrative single-cell analyses.

Zhou B, Huang H, Ding Z, Luo K, Chen Y, Han Y Cell Mol Life Sci. 2025; 82(1):106.

PMID: 40067455 PMC: 11896952. DOI: 10.1007/s00018-025-05597-w.

Functionalized zeolite regulates bone metabolic microenvironment.

Xu M, Liu H, Zhang J, Xu M, Zhao X, Wang J Mater Today Bio. 2025; 31:101558.

PMID: 40034985 PMC: 11874869. DOI: 10.1016/j.mtbio.2025.101558.

Communication between endothelial cells and osteoblasts in regulation of bone homeostasis: Notch players.

Perepletchikova D, Malashicheva A Stem Cell Res Ther. 2025; 16(1):56.

PMID: 39920854 PMC: 11806792. DOI: 10.1186/s13287-025-04176-x.

A transgenic mouse line with a 58 kb fragment deletion shows skeletal defects.

Alamoudi A, Husein D, Ohyama Y, Chen A, Mochida H, Mochida Y Sci Rep. 2025; 15(1):4476.

PMID: 39915545 PMC: 11802833. DOI: 10.1038/s41598-025-88559-3.

References

Yadav V, Oury F, Suda N, Liu Z, Gao X, Confavreux C . A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009; 138(5):976-89. PMC: 2768582. DOI: 10.1016/j.cell.2009.06.051. View

Staehling-Hampton K, Proll S, Paeper B, Zhao L, Charmley P, Brown A . A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet. 2002; 110(2):144-52. DOI: 10.1002/ajmg.10401. View

Hesse E, Saito H, Kiviranta R, Correa D, Yamana K, Neff L . Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity. J Cell Biol. 2010; 191(7):1271-83. PMC: 3010073. DOI: 10.1083/jcb.201009107. View

Calvi L, Adams G, Weibrecht K, Weber J, Olson D, Knight M . Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425(6960):841-6. DOI: 10.1038/nature02040. View

Devlin R, Du Z, Pereira R, Kimble R, Economides A, Jorgetti V . Skeletal overexpression of noggin results in osteopenia and reduced bone formation. Endocrinology. 2003; 144(5):1972-8. DOI: 10.1210/en.2002-220918. View

Giustina A, Mazziotti G, Canalis E . Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev. 2008; 29(5):535-59. PMC: 2726838. DOI: 10.1210/er.2007-0036. View

Otto F, Thornell A, Crompton T, Denzel A, Gilmour K, Rosewell I . Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell. 1997; 89(5):765-71. DOI: 10.1016/s0092-8674(00)80259-7. View

Kamiya N, Ye L, Kobayashi T, Mochida Y, Yamauchi M, Kronenberg H . BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway. Development. 2008; 135(22):3801-11. PMC: 2694443. DOI: 10.1242/dev.025825. View

Wang X, Kua H, Hu Y, Guo K, Zeng Q, Wu Q . p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling. J Cell Biol. 2005; 172(1):115-25. PMC: 2063539. DOI: 10.1083/jcb.200507106. View

10.

Feng X, Derynck R . Specificity and versatility in tgf-beta signaling through Smads. Annu Rev Cell Dev Biol. 2005; 21:659-93. DOI: 10.1146/annurev.cellbio.21.022404.142018. View

11.

Hong J, Hwang E, McManus M, Amsterdam A, Tian Y, Kalmukova R . TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science. 2005; 309(5737):1074-8. DOI: 10.1126/science.1110955. View

12.

Zhang M, Xuan S, Bouxsein M, von Stechow D, Akeno N, Faugere M . Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J Biol Chem. 2002; 277(46):44005-12. DOI: 10.1074/jbc.M208265200. View

13.

Morikawa S, Mabuchi Y, Kubota Y, Nagai Y, Niibe K, Hiratsu E . Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med. 2009; 206(11):2483-96. PMC: 2768869. DOI: 10.1084/jem.20091046. View

14.

Guo J, Liu M, Yang D, Bouxsein M, Saito H, Galvin R . Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation. Cell Metab. 2010; 11(2):161-71. PMC: 2819982. DOI: 10.1016/j.cmet.2009.12.007. View

15.

Vidal O, Lindberg M, Hollberg K, Baylink D, Andersson G, Lubahn D . Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice. Proc Natl Acad Sci U S A. 2000; 97(10):5474-9. PMC: 25853. DOI: 10.1073/pnas.97.10.5474. View

16.

Pignolo R, Kassem M . Circulating osteogenic cells: implications for injury, repair, and regeneration. J Bone Miner Res. 2011; 26(8):1685-93. DOI: 10.1002/jbmr.370. View

17.

Cui C, Cooper L, Yang X, Karsenty G, Aukhil I . Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ. Mol Cell Biol. 2003; 23(3):1004-13. PMC: 140696. DOI: 10.1128/MCB.23.3.1004-1013.2003. View

18.

Mohamed S, Aherrahrou Z, Liptau H, Erasmi A, Hagemann C, Wrobel S . Novel missense mutations (p.T596M and p.P1797H) in NOTCH1 in patients with bicuspid aortic valve. Biochem Biophys Res Commun. 2006; 345(4):1460-5. DOI: 10.1016/j.bbrc.2006.05.046. View

19.

Herreman A, Hartmann D, Annaert W, Saftig P, Craessaerts K, Serneels L . Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency. Proc Natl Acad Sci U S A. 1999; 96(21):11872-7. PMC: 18379. DOI: 10.1073/pnas.96.21.11872. View

20.

Jones D, Wein M, Oukka M, Hofstaetter J, Glimcher M, Glimcher L . Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3. Science. 2006; 312(5777):1223-7. DOI: 10.1126/science.1126313. View