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MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes.
Cell Physiol Biochem. 2017; 44(1):38-52.CP

Abstract

BACKGROUND/AIMS

Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) are secreted enzymes belonging to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family that play significant roles in the progression of osteoarthritis (OA). Here, we aimed to determine whether the expression of ADAMTS-4/5 in chondrogenesis and inflammation is regulated by microRNA-92a-3p (miR-92a-3p).

METHODS

MiR-92a-3p and ADAMTS-4/5 expressions were determined by quantitative polymerase chain reaction (qPCR). To investigate the repressive effect of miR-92a-3p on ADAMTS-4/5 expression, chondrogenic human mesenchymal stem cells (hMSCs) and human chondrocytes were transfected with mature miR-92a-3p or an antisense inhibitor (anti-miR-92a-3p), respectively. ADAMTS-4/5 protein production was quantified by enzyme-linked immunosorbent assay (ELISA), and miR-92a-3p involvement in IL-1β-mediated catabolic effects was examined by immunoblotting. The roles of activated MAP kinases (MAPK) and nuclear factor (NF)-κB were evaluated by using specific inhibitors. Interaction between miR-92a-3p and its putative binding site in the 3'-untranslated region (3'-UTR) of ADAMTS-4/5 mRNA was confirmed by luciferase reporter assay.

RESULTS

miR-92a-3p expression was elevated in chondrogenic hMSCs, with significantly lower expression in OA cartilage than in normal cartilage. Stimulation with IL-1β significantly reduced miR-92a-3p expression in primary human chondrocytes (PHCs). Transfection of chondrocytes with miR-92a-3p downregulated IL-1β-induced ADAMTS-4/5 expression, and the activity of a reporter construct containing the 3'-UTR of human ADAMTS-4/5 mRNA. MiR-92a-3p expression was suppressed upon IL-1β-induced activation of MAPK and NF-κB in chondrocytes.

CONCLUSION

MiR-92a-3p is an important regulator of ADAMTS-4/5 in human chondrocytes and may contribute to the development of OA.

Authors+Show Affiliations

Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.Tower Hill School, Wilmington, Delaware, USA.Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29241192

Citation

Mao, Guping, et al. "MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 44, no. 1, 2017, pp. 38-52.
Mao G, Wu P, Zhang Z, et al. MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes. Cell Physiol Biochem. 2017;44(1):38-52.
Mao, G., Wu, P., Zhang, Z., Zhang, Z., Liao, W., Li, Y., & Kang, Y. (2017). MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 44(1), 38-52. https://doi.org/10.1159/000484579
Mao G, et al. MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes. Cell Physiol Biochem. 2017;44(1):38-52. PubMed PMID: 29241192.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes. AU - Mao,Guping, AU - Wu,Peihui, AU - Zhang,Ziji, AU - Zhang,Zhiqi, AU - Liao,Weiming, AU - Li,Yukang, AU - Kang,Yan, Y1 - 2017/11/03/ PY - 2017/07/07/received PY - 2017/09/29/accepted PY - 2017/12/15/pubmed PY - 2018/3/7/medline PY - 2017/12/15/entrez KW - Aggrecanase-1 KW - Aggrecanase-2 KW - Chondrocytes KW - Chondrogenesis KW - Mirna-92a-3p KW - Osteoarthritis SP - 38 EP - 52 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell Physiol Biochem VL - 44 IS - 1 N2 - BACKGROUND/AIMS: Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) are secreted enzymes belonging to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family that play significant roles in the progression of osteoarthritis (OA). Here, we aimed to determine whether the expression of ADAMTS-4/5 in chondrogenesis and inflammation is regulated by microRNA-92a-3p (miR-92a-3p). METHODS: MiR-92a-3p and ADAMTS-4/5 expressions were determined by quantitative polymerase chain reaction (qPCR). To investigate the repressive effect of miR-92a-3p on ADAMTS-4/5 expression, chondrogenic human mesenchymal stem cells (hMSCs) and human chondrocytes were transfected with mature miR-92a-3p or an antisense inhibitor (anti-miR-92a-3p), respectively. ADAMTS-4/5 protein production was quantified by enzyme-linked immunosorbent assay (ELISA), and miR-92a-3p involvement in IL-1β-mediated catabolic effects was examined by immunoblotting. The roles of activated MAP kinases (MAPK) and nuclear factor (NF)-κB were evaluated by using specific inhibitors. Interaction between miR-92a-3p and its putative binding site in the 3'-untranslated region (3'-UTR) of ADAMTS-4/5 mRNA was confirmed by luciferase reporter assay. RESULTS: miR-92a-3p expression was elevated in chondrogenic hMSCs, with significantly lower expression in OA cartilage than in normal cartilage. Stimulation with IL-1β significantly reduced miR-92a-3p expression in primary human chondrocytes (PHCs). Transfection of chondrocytes with miR-92a-3p downregulated IL-1β-induced ADAMTS-4/5 expression, and the activity of a reporter construct containing the 3'-UTR of human ADAMTS-4/5 mRNA. MiR-92a-3p expression was suppressed upon IL-1β-induced activation of MAPK and NF-κB in chondrocytes. CONCLUSION: MiR-92a-3p is an important regulator of ADAMTS-4/5 in human chondrocytes and may contribute to the development of OA. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/29241192/MicroRNA_92a_3p_Regulates_Aggrecanase_1_and_Aggrecanase_2_Expression_in_Chondrogenesis_and_IL_1β_Induced_Catabolism_in_Human_Articular_Chondrocytes_ L2 - https://www.karger.com?DOI=10.1159/000484579 DB - PRIME DP - Unbound Medicine ER -