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Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression.
Sci Rep 2016; 6:25401SR

Abstract

The mechanical environment is crucial for intervertebral disc degeneration (IDD). However, the mechanisms underlying the regulation of cartilage endplate (CEP) calcification by altered matrix stiffness remain unclear. In this study, we found that matrix stiffness of CEP was positively correlated with the degree of IDD, and stiff matrix, which mimicked the severe degeneration of CEP, promoted inorganic phosphate-induced calcification in CEP chondrocytes. Co-expression analysis of the miRNA and mRNA profiles showed that increasing stiffness resulted in up-regulation of miR-20a and down-regulation of decreased ankylosis protein homolog (ANKH) during inorganic phosphate-induced calcification in CEP chondrocytes. Through a dual luciferase reporter assay, we confirmed that miR-20a directly targets 3'-untranslated regions of ANKH. The inhibition of miR-20a attenuated the calcium deposition and calcification-related gene expression, whereas the overexpression of miR-20a enhanced calcification in CEP chondrocytes on stiff matrix. The rescue of ANKH expression restored the decreased pyrophosphate efflux and inhibited calcification. In clinical samples, the levels of ANKH expression were inversely associated with the degeneration degree of CEP. Thus, our findings demonstrate that the miR-20a/ANKH axis mediates the stiff matrix- promoted CEP calcification, suggesting that miR-20a and ANKH are potential targets in restraining the progression of IDD.

Authors+Show Affiliations

Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China. Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China. Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University, Chongqing, People's Republic of China.Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27142968

Citation

Liu, Ming-Han, et al. "Matrix Stiffness Promotes Cartilage Endplate Chondrocyte Calcification in Disc Degeneration Via miR-20a Targeting ANKH Expression." Scientific Reports, vol. 6, 2016, p. 25401.
Liu MH, Sun C, Yao Y, et al. Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression. Sci Rep. 2016;6:25401.
Liu, M. H., Sun, C., Yao, Y., Fan, X., Liu, H., Cui, Y. H., ... Zhou, Y. (2016). Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression. Scientific Reports, 6, p. 25401. doi:10.1038/srep25401.
Liu MH, et al. Matrix Stiffness Promotes Cartilage Endplate Chondrocyte Calcification in Disc Degeneration Via miR-20a Targeting ANKH Expression. Sci Rep. 2016 05 4;6:25401. PubMed PMID: 27142968.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression. AU - Liu,Ming-Han, AU - Sun,Chao, AU - Yao,Yuan, AU - Fan,Xin, AU - Liu,Huan, AU - Cui,You-Hong, AU - Bian,Xiu-Wu, AU - Huang,Bo, AU - Zhou,Yue, Y1 - 2016/05/04/ PY - 2015/12/07/received PY - 2016/04/18/accepted PY - 2016/5/5/entrez PY - 2016/5/5/pubmed PY - 2018/2/2/medline SP - 25401 EP - 25401 JF - Scientific reports JO - Sci Rep VL - 6 N2 - The mechanical environment is crucial for intervertebral disc degeneration (IDD). However, the mechanisms underlying the regulation of cartilage endplate (CEP) calcification by altered matrix stiffness remain unclear. In this study, we found that matrix stiffness of CEP was positively correlated with the degree of IDD, and stiff matrix, which mimicked the severe degeneration of CEP, promoted inorganic phosphate-induced calcification in CEP chondrocytes. Co-expression analysis of the miRNA and mRNA profiles showed that increasing stiffness resulted in up-regulation of miR-20a and down-regulation of decreased ankylosis protein homolog (ANKH) during inorganic phosphate-induced calcification in CEP chondrocytes. Through a dual luciferase reporter assay, we confirmed that miR-20a directly targets 3'-untranslated regions of ANKH. The inhibition of miR-20a attenuated the calcium deposition and calcification-related gene expression, whereas the overexpression of miR-20a enhanced calcification in CEP chondrocytes on stiff matrix. The rescue of ANKH expression restored the decreased pyrophosphate efflux and inhibited calcification. In clinical samples, the levels of ANKH expression were inversely associated with the degeneration degree of CEP. Thus, our findings demonstrate that the miR-20a/ANKH axis mediates the stiff matrix- promoted CEP calcification, suggesting that miR-20a and ANKH are potential targets in restraining the progression of IDD. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/27142968/Matrix_stiffness_promotes_cartilage_endplate_chondrocyte_calcification_in_disc_degeneration_via_miR_20a_targeting_ANKH_expression_ L2 - http://dx.doi.org/10.1038/srep25401 DB - PRIME DP - Unbound Medicine ER -