Latexin is involved in bone morphogenetic protein-2-induced chondrocyte differentiation |
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| Authors: | Ichiro Kadouchi Kei Sakamoto Liu Tangjiao Takashi Murakami Eiji Kobayashi Yuichi Hoshino Akira Yamaguchi |
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| Institution: | 1. Growth and Development Research Center, Children Medical Hospital, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Medical Genetics, Shahid Beheshti University of Medical sciences, Tehran, Iran;3. Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;4. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran;1. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA;2. Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan;3. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA;1. Department of Orthopaedic Surgery, Washington University, St Louis MO, USA;2. Department of Cell Biology & Physiology, Washington University, St Louis MO, USA;3. Department of Orthopaedic & Sports Medicine, University of Washington, Seattle WA, USA;4. Institute for Physiological Chemistry and Pathobiochemistry, University of Münster, Germany |
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| Abstract: | 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. |
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