title: Cdc42 is critical for cartilage development during endochondral ossification.
abstract: Cdc42 is a widely expressed protein that belongs to the family of Rho GTPases and controls a broad variety of signal transduction pathways in a variety of cell types. To investigate the physiological functions of Cdc42 during cartilage development, we generated chondrocyte-specific inactivated Cdc42 mutant mice (Cdc42(fl/fl); Col2-Cre). The gross morphology of mutant neonates showed shorter limbs and body as compared with the control mice (Cdc42(fl/fl)). Skeletal preparations stained with alcian blue and alizarin red also revealed that the body and the long bone length of the mutants were shorter than those of the control mice. Furthermore, severe defects were found in growth plate chondrocytes in the femur sections of mutant mice, characterized by a reduced proliferating zone height, wider hypertrophic zone, and loss of columnar organization in proliferating chondrocytes. The expression levels of chondrocyte marker genes, such as Col2, Col10, and Mmp13, in mutant mice were decreased as compared with the control mice. Mineralization of trabecular bones in the femur sections was also decreased in the mutants as compared with control mice, whereas osteoid volume was increased. Together these results suggested that chondrocyte proliferation and differentiation in growth plates in the present mutant mice were not normally organized, which contributed to abnormal bone formation. We concluded that Cdc42 is essential for cartilage development during endochondral bone formation.
authors.affiliation: Departments of Biochemistry (W.S., A.Y., R.A., D.S., M.N., R.N., R.K.), Prosthodontics (W.S., K.B.), Periodontology (R.A., M.Y.), and Orthodontics (M.N., R.N., K.M.), School of Dentistry, Showa University, Tokyo 142-8555, Japan; Laboratory of Animal Resources (H.K., T.H., A.A.), Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; and Department of Physiology and Cell Biology (S.T.), Tokyo Medical and Dental University Graduate School and Faculty of Medicine, Tokyo 101-0062, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Suzuki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamada
authors.forename: Ryo
authors.initials: R
authors.lastname: Aizawa
authors.forename: Dai
authors.initials: D
authors.lastname: Suzuki
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kassai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Harada
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Nakayama
authors.forename: Ryo
authors.initials: R
authors.lastname: Nagahama
authors.forename: Koutaro
authors.initials: K
authors.lastname: Maki
authors.forename: Shu
authors.initials: S
authors.lastname: Takeda
authors.forename: Matsuo
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Atsu
authors.initials: A
authors.lastname: Aiba
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Baba
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kamijo
mesh_terms: D000818:Animals; D001846:Bone Development / Q000502:physiology*; D002356:Cartilage / Q000254:growth & development* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005819:Genetic Markers; D006132:Growth Plate; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D010010:Osteoclasts; D011401:Promoter Regions, Genetic; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D005819:Genetic Markers; C045073:Cre recombinase; D019426:Integrases; D020764:cdc42 GTP-Binding Protein