VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation - PubMed (original) (raw)
VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation
H P Gerber et al. Nat Med. 1999 Jun.
Abstract
Hypertrophic chondrocytes in the epiphyseal growth plate express the angiogenic protein vascular endothelial growth factor (VEGF). To determine the role of VEGF in endochondral bone formation, we inactivated this factor through the systemic administration of a soluble receptor chimeric protein (Flt-(1-3)-IgG) to 24-day-old mice. Blood vessel invasion was almost completely suppressed, concomitant with impaired trabecular bone formation and expansion of hypertrophic chondrocyte zone. Recruitment and/or differentiation of chondroclasts, which express gelatinase B/matrix metalloproteinase-9, and resorption of terminal chondrocytes decreased. Although proliferation, differentiation and maturation of chondrocytes were apparently normal, resorption was inhibited. Cessation of the anti-VEGF treatment was followed by capillary invasion, restoration of bone growth, resorption of the hypertrophic cartilage and normalization of the growth plate architecture. These findings indicate that VEGF-mediated capillary invasion is an essential signal that regulates growth plate morphogenesis and triggers cartilage remodeling. Thus, VEGF is an essential coordinator of chondrocyte death, chondroclast function, extracellular matrix remodeling, angiogenesis and bone formation in the growth plate.
Comment in
- Cartilage to bone--angiogenesis leads the way.
Harper J, Klagsbrun M. Harper J, et al. Nat Med. 1999 Jun;5(6):617-8. doi: 10.1038/9460. Nat Med. 1999. PMID: 10371495 No abstract available.
Similar articles
- Cartilage to bone--angiogenesis leads the way.
Harper J, Klagsbrun M. Harper J, et al. Nat Med. 1999 Jun;5(6):617-8. doi: 10.1038/9460. Nat Med. 1999. PMID: 10371495 No abstract available. - The splice variants VEGF121 and VEGF189 of the angiogenic peptide vascular endothelial growth factor are expressed in osteoarthritic cartilage.
Pufe T, Petersen W, Tillmann B, Mentlein R. Pufe T, et al. Arthritis Rheum. 2001 May;44(5):1082-8. doi: 10.1002/1529-0131(200105)44:5<1082::AID-ANR188>3.0.CO;2-X. Arthritis Rheum. 2001. PMID: 11352239 - Possible involvement of VEGF-FLT tyrosine kinase receptor system in normal and tumor angiogenesis.
Shibuya M, Seetharam L, Ishii Y, Sawano A, Gotoh N, Matsushime H, Yamaguchi S. Shibuya M, et al. Princess Takamatsu Symp. 1994;24:162-70. Princess Takamatsu Symp. 1994. PMID: 8983073 Review. - 1Alpha,25-dihydroxyvitamin D3 promotes vascularization of the chondro-osseous junction by stimulating expression of vascular endothelial growth factor and matrix metalloproteinase 9.
Lin R, Amizuka N, Sasaki T, Aarts MM, Ozawa H, Goltzman D, Henderson JE, White JH. Lin R, et al. J Bone Miner Res. 2002 Sep;17(9):1604-12. doi: 10.1359/jbmr.2002.17.9.1604. J Bone Miner Res. 2002. PMID: 12211430 - The skeleton: a multi-functional complex organ: the growth plate chondrocyte and endochondral ossification.
Mackie EJ, Tatarczuch L, Mirams M. Mackie EJ, et al. J Endocrinol. 2011 Nov;211(2):109-21. doi: 10.1530/JOE-11-0048. Epub 2011 Jun 3. J Endocrinol. 2011. PMID: 21642379 Review.
Cited by
- Human bone tissue-derived ECM hydrogels: Controlling physicochemical, biochemical, and biological properties through processing parameters.
Kim YH, Cidonio G, Kanczler JM, Oreffo RO, Dawson JI. Kim YH, et al. Bioact Mater. 2024 Sep 23;43:114-128. doi: 10.1016/j.bioactmat.2024.09.007. eCollection 2025 Jan. Bioact Mater. 2024. PMID: 39376928 Free PMC article. - The role of vascular and lymphatic networks in bone and joint homeostasis and pathology.
Huang J, Liao C, Yang J, Zhang L. Huang J, et al. Front Endocrinol (Lausanne). 2024 Sep 11;15:1465816. doi: 10.3389/fendo.2024.1465816. eCollection 2024. Front Endocrinol (Lausanne). 2024. PMID: 39324127 Free PMC article. Review. - Critical signaling molecules in the temporomandibular joint osteoarthritis under different magnitudes of mechanical stimulation.
Liu Y, Jia F, Li K, Liang C, Lin X, Geng W, Li Y. Liu Y, et al. Front Pharmacol. 2024 Jul 11;15:1419494. doi: 10.3389/fphar.2024.1419494. eCollection 2024. Front Pharmacol. 2024. PMID: 39055494 Free PMC article. Review. - FOXC1 and FOXC2 regulate growth plate chondrocyte maturation towards hypertrophy in the embryonic mouse limb skeleton.
Almubarak A, Zhang Q, Zhang CH, Abdelwahab N, Kume T, Lassar AB, Berry FB. Almubarak A, et al. Development. 2024 Aug 15;151(16):dev202798. doi: 10.1242/dev.202798. Epub 2024 Aug 22. Development. 2024. PMID: 39012257 Free PMC article. - Relationships between matrix mineralization, oxidative metabolism, and mitochondrial structure during ATDC5 murine chondroprogenitor cell line differentiation.
Blank K, Ekanayake D, Cooke M, Bragdon B, Hussein A, Gerstenfeld L. Blank K, et al. J Cell Physiol. 2024 Aug;239(8):e31285. doi: 10.1002/jcp.31285. Epub 2024 Jun 11. J Cell Physiol. 2024. PMID: 38860464
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources