title: RB1CC1 protein suppresses type II collagen synthesis in chondrocytes and causes dwarfism.
abstract: RB1-inducible coiled-coil 1 (RB1CC1) functions in various processes, such as cell growth, differentiation, senescence, apoptosis, and autophagy. The conditional transgenic mice with cartilage-specific RB1CC1 excess that were used in the present study were made for the first time by the Cre-loxP system. Cartilage-specific RB1CC1 excess caused dwarfism in mice without causing obvious abnormalities in endochondral ossification and subsequent skeletal development from embryo to adult. In vitro and in vivo analysis revealed that the dwarf phenotype in cartilaginous RB1CC1 excess was induced by reductions in the total amount of cartilage and the number of cartilaginous cells, following suppressions of type II collagen synthesis and Erk1/2 signals. In addition, we have demonstrated that two kinds of SNPs (T-547C and C-468T) in the human RB1CC1 promoter have significant influence on the self-transcriptional level. Accordingly, human genotypic variants of RB1CC1 that either stimulate or inhibit RB1CC1 transcription in vivo may cause body size variations.
authors: Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; Department of Orthopedic Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors: Ichiro
authors: I
authors: Nishimura
authors: Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan. Electronic address: chano@belle.shiga-med.ac.jp.
authors: Tokuhiro
authors: T
authors: Chano
authors: Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors: Hiroko
authors: H
authors: Kita
authors: Department of Orthopedic Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors: Yoshitaka
authors: Y
authors: Matsusue
authors: Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
authors: Hidetoshi
authors: H
authors: Okabe
mesh_terms: D000818:Animals; D000071183:Autophagy-Related Proteins; D049628:Body Size; D002356:Cartilage / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology*; D024043:Collagen Type II / Q000378:metabolism*; D003433:Crosses, Genetic; D004392:Dwarfism / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
chemical_list: D000071183:Autophagy-Related Proteins; D024043:Collagen Type II; D047908:Intracellular Signaling Peptides and Proteins; C407704:RB1CC1 protein, human; C428743:Rb1cc1 protein, mouse; D011505:Protein-Tyrosine Kinases; C535150:MAPK1 protein, human; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3