title: Regulation of Chondrocyte Survival in Mouse Articular Cartilage by p63.
abstract: Transcription factor p63, of the p53 family, regulates cell proliferation, survival, and apoptosis in various cells and tissues. This study was undertaken to examine the expression and roles of p63 transcript variants in the mouse growth plate and articular chondrocytes.
  
  
  
  For in vivo analyses, we generated Cre-mediated TAp63α-transgenic and TAp63γ-transgenic mice. To induce tissue-specific overexpression or deletion in chondrocytes, chondroprogenitor cells, or early limb bud mesenchymal cells, we used Col2a1-Cre, Sox9-Cre, and Prx1-Cre mice, respectively. We analyzed osteoarthritis (OA) development with aging or surgically induced instability in Prx1-Cre;p63fl/fl(P-conditional knockout) mice.
  
  
  
  Among major variants, TAp63α and TAp63γ are highly expressed in mouse primary costal and articular chondrocytes. The p63 protein was predominantly localized in the hypertrophic zone of the embryonic limb cartilage, and in the middle zone of articular cartilage. No obvious change was observed in skeletal growth of TAp63α-transgenic mice, Sox9-Cre;p63fl/fl, or P-conditional knockout mice, while that of TAp63γ-transgenic mice was impaired due to ectopic apoptosis and the resulting decreased number of chondrocytes. Expression of proapoptotic genes including bax, noxa, puma, and fas was increased in TAp63γ-transgenic mouse chondrocytes, and their transcription was probably sustained by p53 in p63-conditional knockout mouse chondrocytes because both proteins were coexpressed in the growth plate. In contrast, p53 was expressed in the superficial zone of articular cartilage, differently from p63. Notably, P-conditional knockout mice showed significant resistance to OA development, with suppression of chondrocyte apoptosis in the aging and surgical models.
  
  
  
  We demonstrated regulation of chondrocyte survival in articular cartilage by p63.
authors: University of Tokyo, Tokyo, Japan.
authors: Yuki
authors: Y
authors: Taniguchi
authors: University of Tokyo, Tokyo, Japan.
authors: Manabu
authors: M
authors: Kawata
authors: University of Tokyo, Tokyo, Japan.
authors: Song
authors: S
authors: Ho Chang
authors: University of Tokyo, Tokyo, Japan.
authors: Daisuke
authors: D
authors: Mori
authors: University of Tokyo, Tokyo, Japan.
authors: Keita
authors: K
authors: Okada
authors: University of Tokyo, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Kobayashi
authors: University of Tokyo, Tokyo, Japan.
authors: Shurei
authors: S
authors: Sugita
authors: University of Tokyo, Tokyo, Japan.
authors: Yoko
authors: Y
authors: Hosaka
authors: University of Tokyo, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Inui
authors: University of Tokyo, Tokyo, Japan.
authors: Shuji
authors: S
authors: Taketomi
authors: University of Tokyo, Tokyo, Japan.
authors: Fumiko
authors: F
authors: Yano
authors: University of Tokyo, Tokyo, Japan.
authors: Toshiyuki
authors: T
authors: Ikeda
authors: Gifu University, Gifu, Japan.
authors: Haruhiko
authors: H
authors: Akiyama
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
authors: Alea A
authors: AA
authors: Mills
authors: University of Tokyo, Tokyo, Japan.
authors: Ung-Il
authors: UI
authors: Chung
authors: University of Tokyo, Tokyo, Japan.
authors: Sakae
authors: S
authors: Tanaka
authors: University of Tokyo and Tokyo Shinjuku Medical Center, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Kawaguchi
authors: University of Tokyo, Tokyo, Japan.
authors: Taku
authors: T
authors: Saito
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology*; D002470:Cell Survival; D019902:Chondrocytes / Q000502:physiology*; D006132:Growth Plate / Q000166:cytology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*
chemical_list: D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse