Rho GTPase protein Cdc42 is critical for postnatal cartilage development.
Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 (fl/fl); Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 (fl/fl)) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages.
['Nagahama|Ryo|R|', 'Yamada|Atsushi|A|', 'Tanaka|Junichi|J|', 'Aizawa|Ryo|R|', 'Suzuki|Dai|D|', 'Kassai|Hidetoshi|H|', 'Yamamoto|Matsuo|M|', 'Mishima|Kenji|K|', 'Aiba|Atsu|A|', 'Maki|Koutaro|K|', 'Kamijo|Ryutaro|R|']
D000818:Animals D000831:Animals, Newborn D049628:Body Size D002356:Cartilage D049109:Cell Proliferation D048429:Cell Size D002478:Cells, Cultured D019902:Chondrocytes D018507:Gene Expression Regulation, Developmental D051379:Mice D008817:Mice, Mutant Strains D008822:Mice, Transgenic D020764:cdc42 GTP-Binding Protein
Cdc42 Cartilage Col2-CreERT transgenic mice