Pancras CW Hogendoorn, Leiden University Medical Centre, Leiden, The Netherlands
Judith VMG Bovée, Leiden University Medical Centre, Leiden, The Netherlands
Marcel Karperien, Leiden University Medical Centre, Leiden, The Netherlands
Anne‐Marie Cleton‐Jansen, Leiden University Medical Centre, Leiden, The Netherlands
Published online: January 2006
DOI: 10.1038/npg.els.0005996
Skeletogenesis is a tightly regulated process during fetal, postnatal and pubertal growth, finely orchestrated by transcription factors and consecutive signaling pathways and controlled by delicate feedback loops. There is an increasing awareness of the role of these processes during tumorigenesis of primary bone tumors.
Keywords: bone; bone neoplasm; growth regulation; chondrosarcoma; osteosarcoma; bone formation; osteoblast; chondrocyte; osteoclast
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Figure 1. Overview of genes involved in the three cellular lineages that contribute to skeletogenesis: osteoblasts, chondrocytes and osteoclasts. The genes that are involved in the distinct differentiation stages are shown.
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Figure 2. Anatomy of long bones.
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Figure 3. Signaling pathway operative in the early embryonic growth plate and postnatal growth plate respectively. Note substantial differences in growth regulation during development. The paracrine feedback loop involving parathyroid hormone-related peptide (PTHrP) is shown in the embryonic and the postnatal growth plate. Associated molecules are shown in bold. Proteins: CycE/D: cyclin E, -D; EXT1/2: exostosin 1, -2; FGF18: fibroblast growth factor 18; FGFR3: FGF receptor 3; HSPG: heparan sulfate proteoglycan; IHh: Indian hedgehog; Ptc: patched.
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| References | |
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| Further Reading | |
| Bi W, Deng JM, Zhang Z, Behringer RR and de Crombrugghe B (1999) Sox9 is required for cartilage formation. Nature Genetics 22: 85–89. | |
| Capdevila J and Izpisua Belmonte JC (2001) Patterning mechanisms controlling vertebrate limb development. Annual Review of Cell and Developmental Biology 17: 87–132. | |
| Chung UI, Schipani E, McMahon AP and Kronenberg HM (2001) Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development. Journal of Clinical Investigation 107: 295–304. | |
| Hartmann C and Tabin CJ (2000) Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development 127: 3141–3159. | |
| Jochum W, David JP, Elliott C, et al. (2000) Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1. Nature Medicine 6: 980–984. | |
| Karp SJ, Schipani E, St Jacques B, et al. (2000) Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways. Development 127: 543–548. | |
| Karsenty G (1999) The genetic transformation of bone biology. Genes & Development 13: 3037–3051. | |
| Le Roith D, Bondy C, Yakar S, Liu JL and Butler A (2001) The somatomedin hypothesis: 2001. Endocrinology Review 22: 53–74. | |
| Sabatakos G, Sims NA, Chen J, et al. (2000) Overexpression of DeltaFosB transcription factor(s) increases bone formation and inhibits adipogenesis. Nature Medicine 6: 985–990. | |
| The I, Bellaiche Y and Perrimon N (1999) Hedgehog movement is regulated through tout velu-dependant synthesis of a heparan sulfate proteoglycan. Molecular Cell 4: 633–639. | |
| Tsumaki N, Nakase T, Miyaji T, et al. (2002) Bone morphogenetic protein signals are required for cartilage formation and differently regulate joint development during skeletogenesis. Journal of Bone Mineral Research: The Official Journal of the American Society for Bone and Mineral Research 17: 898–906. | |
| Wuyts W, Van Wesenbeeck L, Morales-Piga A, et al. (2001) Evaluation of the role of RANK and OPG genes in Paget disease of bone. Bone 28: 104–107. | |
| Web Links | |
| ePath Gene Ontology Tools. The website of the Gene Ontology Consortium aims at producing a dynamic controlled vocabulary that can be applied to all organisms even as knowledge of gene and protein roles in cells is accumulating and changing. http://www.godatabase.org/dev/ | |
| ePath COL1A1(collagen, type I, alpha 1); Locus ID: 1277. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1277 | |
| ePath COL1A1(collagen, type I, alpha 1); MIM number: 120150. OMIM: http://www.ncbi.nlm.nih.gov/-post/Omim/dispmim?120150 | |
| ePath ESR1(estrogen receptor 1); Locus ID: 2099. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2099 | |
| ePath ESR1(estrogen receptor 1); MIM number: 133430. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?133430 | |
| ePath EXT1(exostoses(multiple) 1); Locus ID: 2131. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2131 | |
| ePath EXT1(exostoses(multiple) 1); MIM number: 133700. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?133700 | |
| ePath FGFR3(fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)); Locus ID: 2261. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2261 | |
| ePath FGFR3(fibroblast growth factor receptor 3(achondroplasia, thanatophoric dwarfism)); MIM number: 134934. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?134934 | |
| ePath TNFRSF11A(tumor necrosis factor receptor superfamily, member 11a, activator of NFKB); Locus ID: 8792. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=8792 | |
| ePath TNFRSF11A(tumor necrosis factor receptor superfamily, member 11a, activator of NFKB); MIM number: 603499. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?603499 | |
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