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A molecular analysis of matrix remodeling and angiogenesis during long bone development
Authors:Colnot C I  Helms J A
Institution:Department of Orthopedic Surgery, University of California at San Francisco, CA 94143-0514, USA.
Abstract:The replacement of cartilage by bone is the net result of genetic programs that control chondrocyte differentiation, matrix degradation, and bone formation. Disruptions in the rate, timing, or duration of chondrocyte proliferation and differentiation result in shortened, misshapen skeletal elements. In the majority of these skeletal disruptions, vascular invasion of the elements is also perturbed. Our hypothesis is that the processes involved in endochondral ossification are synchronized via the vasculature. The purpose of this study was to examine carefully the events of vascular invasion and matrix degradation in the context of chondrocyte differentiation and bone formation. Here, we have produced a ‘molecular map’ of the initial vascularization of the developing skeleton that provides a framework in which to interpret a wide range of fetal skeletal malformations, disruptions, and dysplasias.
Keywords:Mouse  Development  Cartilage  Bone  Perichondrium  Hypertrophic chondrocyte  Endochondral ossification  Osteoblast  Osteoclast  Chondroclast  Vascular invasion  Extracellular matrix  Angiogenic factor  Matrix metalloproteinases (MMP)  Tissue inhibitors of MMPs (TIMP)  In situ hybridization  PECAM  TRAP  Vascular endothelial growth factor (VEGF)  Osteocalcin  Osteopontin  Indian hedgehog (IHH)  Bone morphogenetic protein 3 (BMP3)  Neuropilin  MT-MMP  Collagenase  Gelatinase  Collagen type X (10)
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