MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression

Chen, Weishen; Sheng, Puyi; Huang, Zhiyu; Meng, Fangang; Kang, Yan; Huang, Guangxin; Zhang, Zhiqi; Liao, Weiming; Zhang, Ziji

doi:10.3390/ijms17091377

Open AccessArticle

MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression

by

Weishen Chen

^†,

Puyi Sheng

^†,

Zhiyu Huang

,

Fangang Meng

,

Yan Kang

,

Guangxin Huang

,

Zhiqi Zhang

,

Weiming Liao

^* and

Ziji Zhang

^*

Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2016, 17(9), 1377; https://doi.org/10.3390/ijms17091377

Submission received: 29 June 2016 / Revised: 12 August 2016 / Accepted: 16 August 2016 / Published: 23 August 2016

(This article belongs to the Collection Regulation by Non-coding RNAs)

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Abstract

Chondrocyte hypertrophy, regulated by Runt-related transcription factor 2 (RUNX2) and matrix metalloproteinase 13 (MMP13), is a crucial step in cartilage degeneration and osteoarthritis (OA) pathogenesis. We previously demonstrated that microRNA-381 (miR-381) promotes MMP13 expression during chondrogenesis and contributes to cartilage degeneration; however, the mechanism underlying this process remained unclear. In this study, we observed divergent expression of miR-381 and histone deacetylase 4 (HDAC4), an enzyme that directly inhibits RUNX2 and MMP13 expression, during late-stage chondrogenesis of ATDC5 cells, as well as in prehypertrophic and hypertrophic chondrocytes during long bone development in E16.5 mouse embryos. We therefore investigated whether this miRNA regulates HDAC4 expression during chondrogenesis. Notably, overexpression of miR-381 inhibited HDAC4 expression but promoted RUNX2 expression. Moreover, transfection of SW1353 cells with an miR-381 mimic suppressed the activity of a reporter construct containing the 3′-untranslated region (3′-UTR) of HDAC4. Conversely, treatment with a miR-381 inhibitor yielded increased HDAC4 expression and decreased RUNX2 expression. Lastly, knockdown of HDAC4 expression resulted in increased RUNX2 and MMP13 expression in SW1353 cells. Collectively, our results indicate that miR-381 epigenetically regulates MMP13 and RUNX2 expression via targeting of HDAC4, thereby suggesting the possibilities of inhibiting miR-381 to control chondrocyte hypertrophy and cartilage degeneration.

Keywords: microRNA-381; chondrocyte hypertrophy; histone deacetylase 4; Runt-related transcription factor 2; matrix metalloproteinase 13

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MDPI and ACS Style

Chen, W.; Sheng, P.; Huang, Z.; Meng, F.; Kang, Y.; Huang, G.; Zhang, Z.; Liao, W.; Zhang, Z. MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression. Int. J. Mol. Sci. 2016, 17, 1377. https://doi.org/10.3390/ijms17091377

AMA Style

Chen W, Sheng P, Huang Z, Meng F, Kang Y, Huang G, Zhang Z, Liao W, Zhang Z. MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression. International Journal of Molecular Sciences. 2016; 17(9):1377. https://doi.org/10.3390/ijms17091377

Chicago/Turabian Style

Chen, Weishen, Puyi Sheng, Zhiyu Huang, Fangang Meng, Yan Kang, Guangxin Huang, Zhiqi Zhang, Weiming Liao, and Ziji Zhang. 2016. "MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression" International Journal of Molecular Sciences 17, no. 9: 1377. https://doi.org/10.3390/ijms17091377

APA Style

Chen, W., Sheng, P., Huang, Z., Meng, F., Kang, Y., Huang, G., Zhang, Z., Liao, W., & Zhang, Z. (2016). MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression. International Journal of Molecular Sciences, 17(9), 1377. https://doi.org/10.3390/ijms17091377

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MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression

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