Latexin is involved in bone morphogenetic protein-2-induced chondrocyte differentiation

• Published in: Biochemical and biophysical research communications Vol. 378; no. 3; pp. 600 - 604
• Main Authors: Kadouchi, Ichiro, Sakamoto, Kei, Tangjiao, Liu, Murakami, Takashi, Kobayashi, Eiji, Hoshino, Yuichi, Yamaguchi, Akira
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.01.2009
• Subjects: 60 APPLIED LIFE SCIENCES; Aggrecans - genetics; Aggrecans - metabolism; Animals; Antigens - genetics; Antigens - metabolism; BMP-2; Bone fracture; BONE FRACTURES; Bone Morphogenetic Protein 2 - pharmacology; Bone regeneration; Bone Regeneration - genetics; CARBOXYPEPTIDASES; CARTILAGE; Cell Differentiation - genetics; Cell Line; Chondrocyte; Chondrocytes - cytology; Chondrocytes - drug effects; Chondrocytes - metabolism; Collagen Type II - genetics; Collagen Type II - metabolism; Collagen Type X - genetics; Collagen Type X - metabolism; CONNECTIVE TISSUE CELLS; Embryo, Mammalian - metabolism; ENZYME INHIBITORS; Gene Expression Regulation, Developmental; GENES; Latexin; MAMMALS; Mice; Mice, Inbred Strains; Osteogenesis - genetics; Promoter Regions, Genetic; PROMOTERS; REGENERATION; SKELETON; SOX9 Transcription Factor - genetics; SOX9 Transcription Factor - metabolism; Cartilage; Chondrocyte; BMP-2; Latexin; Bone regeneration; Bone fracture
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.11.111

Latexin is the only known carboxypeptidase A inhibitor in mammals. We previously demonstrated that BMP-2 significantly induced latexin expression in Runx2-deficient mesenchymal cells (RD-C6 cells), during chondrocyte and osteoblast differentiation. In this study, we investigated latexin expression in the skeleton and its role in chondrocyte differentiation. Immunohistochemical studies revealed that proliferating and prehypertrophic chondrocytes expressed latexin during skeletogenesis and bone fracture repair. In the early phase of bone fracture, latexin mRNA expression was dramatically upregulated. BMP-2 upregulated the expression of the mRNAs of latexin, Col2a1, and the gene encoding aggrecan ( Agc1) in a micromass culture of C3H10T1/2 cells. Overexpression of latexin additively stimulated the BMP-2-induced expression of the mRNAs of Col2a, Agc1, and Col10a1. BMP-2 treatment upregulated Sox9 expression, and Sox9 stimulated the promoter activity of latexin. These results indicate that latexin is involved in BMP-2-induced chondrocyte differentiation and plays an important role in skeletogenesis and skeletal regeneration.