Reaching a genetic and molecular understanding of skeletal development

Karsenty, Gerard; Wagner, Erwin F.

Affiliations

¹Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030

²IMP—Research Institute of Molecular Pathology, A-1030 Vienna, Austria

Abstract

In the last ten years, we have made considerable progress in our genetic and molecular understanding of all aspects of skeletal development, chondrogenesis, joint formation, and osteogenesis. This review addresses the role of the principal growth factors and transcription factors affecting these different processes and presents, in several cases, the genetic cascade leading to cell differentiation.

Links

DOI: 10.1016/S1534-5807(02)00157-0

PubMed: 11970890

WoS: 000175386100007

History

Revised: 2002-04-1

Online: 2004-04-16

Cited Works (14)

Year	Entry
1997	Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsent G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. May 30, 1997;89(5):747-754.
2001	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 GCM, 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, van den Boogaard M-J, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. November 16, 2001;107(4):513-523.
1999	Bi W, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B. Sox9 is required for cartilage formation. Nat Genet. May 1999;22(1):85-89.
1999	St-Jacques B, Hammerschmidt M, McMahon AP. Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev. August 15, 1999;13(16):2072-2086.
1997	Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao Y-H, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. May 30, 1997;89(5):755-764.
1999	Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. June 1999;20(3):345-357.
1998	Lacey DL, Timms E, Tan H-L, 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 Y-X, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. April 17, 1998;93(2):165-176.
1996	Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabi CJ. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science. August 2, 1996;273(5275):613-622.
2000	Teitelbaum SL. Bone resorption by osteoclasts. Science. September 1, 2000;289(5484):1504-1508.
1997	Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell. May 30, 1997;89(5):765-771.
2002	Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao S-C, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Van Eerdewegh P, Recker RR, Johnson ML. A mutation in the LDL receptor–related protein 5 gene results in the autosomal dominant high–bone-mass trait. Am J Hum Genet. January 2002;70(1):11-19.
2002	Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. January 11, 2002;108(1):17-29.
1999	Gerber H-P, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med. June 1999;5(6):623-628.
2000	Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. April 2000;21(2):115-137.

Cited By (32)

Year	Entry
2008	Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. May 15, 2008;473(2):139-146.
2007	Asagiri M, Takayanagi H. The molecular understanding of osteoclast differentiation. Bone. February 2007;40(2):251-264.
2021	Hensley AP, McAlinden A. The role of microRNAs in bone development. Bone. February 2021;143:115760.
2006	Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Suda T, Matsuo K. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab. August 2006;4(2):111-121.
2007	Tatsumi S, Ishii K, Amizuka N, Li M, Kobayashi T, Kohno K, Ito M, Takeshita S, Ikeda K. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. June 2007;5(6):464-475.
2002	Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J-i, Wagner EF, Mak TW, Kodama T, Taniguchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. December 1, 2002;3(6):889-901.
2005	Hill TP, Später D, Taketo MM, Birchmeier W, Hartmann C. Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell. May 2005;8(5):727-738.
2005	Day TF, Guo X, Garrett-Beal L, Yang Y. Wnt/β-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell. May 2005;8(5):739-750.
2005	Glass DA II, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, Karsenty G. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. May 2005;8(5):751-764.
2010	Maes C, Kobayashi T, Selig MK, Torrekens S, Roth SI, Mackem S, Carmeliet G, Kronenberg HM. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell. August 17, 2010;19(2):329-344.
2014	Mizoguchi T, Pinho S, Ahmed J, Kunisaki Y, Hanoun M, Mendelson A, Ono N, Kronenberg HM, Frenette PS. Osterix marks distinct waves of primitive and definitive stromal progenitors during bone marrow development. Dev Cell. May 12, 2014;29(3):340-349.
2002	Zhang M, Xuan S, Bouxsein ML, von Stechow D, Akeno N, Faugere MC, Malluche H, Zhao G, Rosen CJ, Efstratiadis A, Clemens TL. 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. November 15, 2002;277(46):44005-44012.
2005	Woods A, Wang G, Beier F. RhoA/ROCK signaling regulates Sox9 expression and actin organization during chondrogenesis. J Biol Chem. March 25, 2005;280(12):11626-11634.
2015	Oftadeh R, Perez-Viloria M, Villa-Camacho JC, Vaziri A, Nazarian A. Biomechanics and mechanobiology of trabecular bone: a review. J Biomech Eng. January 2015;137(1):010802.
2004	Judex S, Garman R, Squire M, Donahue L, Rubin C. Genetically based influences on the site‐specific regulation of trabecular and cortical bone morphology. J Bone Miner Res. April 2004;19(4):600-606.
2003	Harada S-i, Rodan GA. Control of osteoblast function and regulation of bone mass. Nature. May 15, 2003;423(6937):349-355.
2012	Song MJ. Elucidating the Mechanical Milieu of Stem Cells in Situ and Delivering Mechanical Signals to Direct Cell Fate in Tissue Engineering Scaffolds [PhD thesis]. Cleveland, OH: Case Western Reserve University; August 2012.
2013	Shekaran A. Beta 1 Integrins in Bone Formation During Development and Engineering Integrin-Specific Hydrogels for Enhanced Bone Healing [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; May 2013.
2019	Lindsey RC. Signaling Pathways in Skeletal Development and Metabolism [PhD thesis]. Loma Linda University; May 2019.
2017	Mathavan N. The Anabolic - Anti-Catabolic Paradigm of Augmenting Skeletal Regeneration: A Bone Quality Perspective [PhD thesis]. Lund, Sweden: Lund University; 2017.
2013	Antolić A. Mitochondrial Contributions to Bone Health, an Investigation Using Two Different Animal Models of Mitochondrial Capacity [PhD thesis]. Hamilton, ON: McMaster University; September 2013.
2009	Landman AS. Pocket Protein Family Function in Mesenchymal Tissue Development and Tumorigenesis [PhD thesis]. Cambridge, MA: Massachusetts Institute of Technology; September 2009.
2015	Oftadeh R. Hierarchical Analysis and Multiscale Modelling of Cellular Structures: From Meta Materials to Bone Structure [PhD thesis]. Northeastern University; December 2015.
2006	Garman RA. Low-Level Accelerations Applied in the Absence of Weight Bearing Can Alter Cellular Activity and Tissue Morphology in the Skeleton [PhD thesis]. Stony Brook, NY: Stony Brook University; May 2006.
2012	Hu M. Mitigation of Bone Loss and Augment of Anabolic Adaptation by Physiological Dynamic Fluid Flow Stimulation [PhD thesis]. Stony Brook, NY: Stony Brook University; December 2012.
2012	Al-Daghreer SM. Analysis of the Biological Effects of Therapeutic Ultrasound on Orthodontically Induced Tooth Root Resorption Repair [PhD thesis]. Edmonton, AB: University of Alberta; 2012.
2013	Newa M. Antibody Mediated “Universal” Osteoclast Targeting Platform [PhD thesis]. Edmonton, AB: University of Alberta; 2013.
2016	Chang N. Structural Deterioration of Human Articular Cartilage and Subchondral Plate [PhD thesis]. San Diego (UCSD), University of California; 2016.
2021	Rivera KO. Localized Neurotrophin Delivery Via Microparticles for Enhanced Bone Fracture Repair [PhD thesis]. San Francisco, University of California; 2021.
2019	Youlten S. Defining the Transcriptome of the Osteocyte Network [PhD thesis]. University of New South Wales; 2019.
2020	Kegelman CD. Combinatorial Roles of Skeletal Cell YAP and TAZ in Bone Growth, Remodeling, and Repair [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2020.
2024	Bell-Hensley A. Epigenetic Regulation of Skeletal Development [PhD thesis]. St. Louis, MO: Washington University in St. Louis; August 2024.