PMID- 30036111 OWN - NLM STAT- MEDLINE DCOM- 20191001 LR - 20191001 IS - 1557-7465 (Electronic) IS - 1079-9907 (Linking) VI - 38 IP - 8 DP - 2018 Aug TI - KLF15 Regulates the Expression of MMP-3 in Human Chondrocytes. PG - 356-362 LID - 10.1089/jir.2017.0135 [doi] AB - Imbalance of metabolism on catabolic and anabolic molecules in chondrocytes has been associated with the cartilage damage in osteoarthritis (OA). Matrix metalloproteinase-3 (MMP-3), one of the most important catabolic factors, acts as a cartilage-degrading enzyme, which is associated with the degradation of type II collagen and aggrecan. Kruppel-like factor 15 (KLF15), an important member of the KLFs family, possesses a variety of biological functions. However, the physiological roles of KLF15 in chondrocytes and the pathological progression of OA remain unknown. In the current study, we report that KLF15 is expressed in primary chondrocytes as well as ATDC5 and SW1353 chondrogenic cell lines. Interestingly, KLF15 expression was significantly lower in chondrocytes from OA patients compared with those from normal subjects. Also, we found that tumor necrosis factor alpha (TNF-alpha) treatment reduced the expression of KLF15 mediated by p53 in human chondrocytes. Notably, it was shown that KLF15 reduced TNF-alpha-induced expression of MMP-3 at the transcriptional level. Mechanistically, the chromatin immunoprecipitation assay displayed that KLF15 could bind to the promoter region of MMP-3. Our results suggest that KLF15 might be a novel therapeutic target of OA. FAU - Li, Yishuo AU - Li Y AD - 1 Department of Rheumatology and Immunology, The First Hospital of China Medical University , Shenyang, China . FAU - Zhao, Min AU - Zhao M AD - 2 Department of Rheumatology and Immunology, The First Affiliated Hospital of Dalian Medical University , Dalian, China . FAU - Xiao, Weiguo AU - Xiao W AD - 1 Department of Rheumatology and Immunology, The First Hospital of China Medical University , Shenyang, China . LA - eng PT - Journal Article DEP - 20180723 PL - United States TA - J Interferon Cytokine Res JT - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research JID - 9507088 RN - 0 (KLF15 protein, human) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (Nuclear Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Cells, Cultured MH - Chondrocytes/*metabolism MH - Dose-Response Relationship, Drug MH - Humans MH - Kruppel-Like Transcription Factors/antagonists & inhibitors/genetics/*metabolism MH - Matrix Metalloproteinase 3/*genetics/metabolism MH - Nuclear Proteins/antagonists & inhibitors/genetics/*metabolism MH - Osteoarthritis/drug therapy/metabolism MH - Tumor Necrosis Factor-alpha/pharmacology OTO - NOTNLM OT - Kruppel-like factor 15 OT - chondrocytes OT - matrix metalloproteinase-3 OT - tumor necrosis factor alpha EDAT- 2018/07/24 06:00 MHDA- 2019/10/02 06:00 CRDT- 2018/07/24 06:00 PHST- 2018/07/24 06:00 [pubmed] PHST- 2019/10/02 06:00 [medline] PHST- 2018/07/24 06:00 [entrez] AID - 10.1089/jir.2017.0135 [doi] PST - ppublish SO - J Interferon Cytokine Res. 2018 Aug;38(8):356-362. doi: 10.1089/jir.2017.0135. Epub 2018 Jul 23.