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Constitutive L-Sox5 overexpression delays differentiation of ATDC5 cells into chondrocytes and correlates with reduced expression of differentiation markers

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Abstract

L-Sox5 is a member of sex-determining region Y-type high mobility group box (SOX) family of transcription factors. We assessed the effects of retroviral overexpression of L-Sox5 on chondrocyte differentiation using the clonal murine cell line ATDC5. We observed a temporal-restricted expression pattern of L-Sox5 in insulin-induced ATDC5 cells differentiating toward chondrocyte lineage. The protein expression levels of L-Sox5 showed a drastic decrease in contrast to unaltered mRNA levels during differentiation. L-Sox5 delayed the differentiation of ATDC5 cells as evidenced by Alcian blue staining for proteoglycan synthesis. The mRNA levels of chondrocyte and hypertrophic/osteoarthritic markers were markedly decreased or delayed in L-Sox5 overexpressing cells. L-Sox5 abrogated the promoter activity of Runx2. These results suggest that L-Sox5 protein expression may diminish along with the progress of chondrogenic differentiation. L-Sox5 may act as a negative regulator if expressed aberrantly at least in part by regulating the critical fate of chondrogenesis.

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Acknowledgments

This work is dedicated to the memory of late Professor S. Hao. The authors thank Drs. T. Komori, V. Lefebvre, and B. de Crombrugghe for providing materials.

Role of funding sources

This work was jointly supported by grants from the National Natural Science Foundation of China (30270660), the Jilin Province Science and Technology Development Project (20040114), the Fok Ying Tung Education Foundation (91025), and the Training Fund of NENU’S Scientific Innovation Project (NENU-STC08015). Neither of the funding agencies played any part in the design or conduct of this study, nor in the analysis of data or preparation of this manuscript.

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The authors declare that they have no conflicts of interests.

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Correspondence to Vishwa Deepak or Wenguang Liu.

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Sun, D., Deepak, V., Mu, P. et al. Constitutive L-Sox5 overexpression delays differentiation of ATDC5 cells into chondrocytes and correlates with reduced expression of differentiation markers. Mol Cell Biochem 401, 21–26 (2015). https://doi.org/10.1007/s11010-014-2288-8

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