title: Rho GTPase protein Cdc42 is critical for postnatal cartilage development.
abstract: 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.
authors.affiliation: Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan; Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nagahama
authors.affiliation: Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan. Electronic address: yamadaa@dent.showa-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Department of Periodontology, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Aizawa
authors.affiliation: Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Suzuki
authors.affiliation: Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kassai
authors.affiliation: Department of Periodontology, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: Matsuo
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Mishima
authors.affiliation: Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Atsu
authors.initials: A
authors.lastname: Aiba
authors.affiliation: Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Maki
authors.affiliation: Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Kamijo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D049628:Body Size / Q000502:physiology*; D002356:Cartilage / Q000166:cytology* / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D048429:Cell Size; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D020764:cdc42 GTP-Binding Protein
keywords: Cartilage; Cdc42; Col2-CreERT transgenic mice