title: Conditional deletion of Tgfbr2 in hypertrophic chondrocytes delays terminal chondrocyte differentiation.
abstract: Transforming growth factor β (Tgfb) signaling plays an important role in endochondral ossification. Previous studies of mice in which the Tgfb type II receptor gene (Tgfbr2) was deleted in the limb bud mesenchymal cells or differentiated chondrocytes showed defects in the development of the long bones or the axial skeleton, respectively. Here, we generated mouse embryos in which the Tgfbr2 gene was ablated in hypertrophic chondrocytes. These mice exhibited delays in both the hypertrophic conversion of proliferating chondrocytes and the subsequent terminal chondrocyte differentiation. The expression domains of Col10a1, Matrix metalloproteinase 13, and Osteopontin were small, and the expression of Vascular endothelial growth factor and Platelet endothelial cell adhesion molecule was downregulated. The calcification of the bone collar in the mutant mice was markedly delayed and the periosteum was thin, possibly because of the downregulation of Indian hedgehog expression. We conclude that Tgfb signaling in hypertrophic chondrocytes positively regulates terminal chondrocyte differentiation, angiogenesis in calcified cartilage, and osteogenesis in the bone collar, at least partly through Indian hedgehog signaling in vivo.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sueyoshi
authors.forename: Koji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006984:Hypertrophy / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010012:Osteogenesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D053773:Transforming Growth Factor beta1 / Q000502:physiology
chemical_list: C570620:Col10a1 protein, mouse; C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D024121:Collagen Type X; D053823:Hedgehog Proteins; D018125:Receptors, Transforming Growth Factor beta; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D053773:Transforming Growth Factor beta1; C514061:ihh protein, mouse; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II