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International Journal of Endocrinology
Volume 2013 (2013), Article ID 679763, 9 pages
http://dx.doi.org/10.1155/2013/679763
Research Article

Dysfunction of Collagen Synthesis and Secretion in Chondrocytes Induced by Wisp3 Mutation

1Institute of Endocrinology and Metabolism, The Second Xiang-Ya Hospital of Central South University, Changsha, Hunan 410011, China
2Department of Endocrinology and Metabolism, Xiang-Ya Hospital of Central South University, Changsha, Hunan 410008, China

Received 23 December 2012; Revised 21 January 2013; Accepted 28 January 2013

Academic Editor: Peng-Fei Shan

Copyright © 2013 Min Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Wisp3 gene mutation was shown to cause spondyloepiphyseal dysplasia tarda with progressive arthropathy (SRDT-PA), but the underlying mechanism is not clear. To clarify this mechanism, we constructed the wild and mutated Wisp3 expression vectors and transfected into human chondrocytes lines C-20/A4; Wisp3 proteins subcellular localization, cell proliferation, cell apoptosis, and Wisp3-mediated gene expression were determined, and dynamic secretion of collagen in transfected chondrocytes was analyzed by 14C-proline incorporation experiment. Mutated Wisp3 protein increased proliferation activity, decreased apoptosis of C-20/A4 cells, and aggregated abnormally in cytoplasm. Expression of collagen II was also downregulated in C-20/A4 cells transfected with mutated Wisp3. Wild type Wisp3 transfection increased intracellular collagen content and extracellular collagen secretion, but the mutated Wisp3 lost this function, and the peak phase of collagen secretion was delayed in mutated Wisp3 transfected cells. Thus abnormal protein distribution, cell proliferation, collagen synthesis, and secretion in Wisp3 mutated chondrocytes might contribute to the pathogenesis of SEDT-PA.