PMID- 35992546 OWN - NLM STAT- MEDLINE DCOM- 20220823 LR - 20221006 IS - 1555-4317 (Electronic) IS - 1555-4309 (Print) IS - 1555-4309 (Linking) VI - 2022 DP - 2022 TI - Circular RNA MELK Promotes Chondrocyte Apoptosis and Inhibits Autophagy in Osteoarthritis by Regulating MYD88/NF-kappaB Signaling Axis through MicroRNA-497-5p. PG - 7614497 LID - 10.1155/2022/7614497 [doi] LID - 7614497 AB - Osteoarthritis (OA) is a rheumatic disease and its pathogenesis involves the dysregulation of noncoding RNAs. Therefore, the regulatory mechanism of circular RNA MELK (circMELK) was specified in this work. OA human cartilage tissue was collected, and circMELK, miR-497-5p, and myeloid differentiation factor 88 (MYD88) expression were examined. Human chondrocytes were stimulated with interleukin- (IL-) 1beta and interfered with vectors altering circMELK, miR-497-5p, and MyD88 expression to observe their effects on cell viability, cell cycle and apoptosis, autophagy, and inflammation. The binding relationship between RNAs was verified. The data presented that OA cartilage tissues presented raised circMELK and MYD88 and inhibited miR-497-5p expression. IL-1beta suppressed cell viability, prevented cell cycle, and induced apoptosis, autophagy, and inflammation of chondrocytes. Functionally, IL-1beta-induced changes of chondrocytes could be attenuated by suppressing circMELK or overexpressing miR-497-5p. circMELK acted as a sponge of miR-497-5p while miR-497-5p was a regulator of MYD88. MYD88 restricted the effect of overexpressing miR-497-5p on IL-1beta-stimulated chondrocytes. MYD88 triggered nuclear factor-kappaB (NF-kappaB) pathway activation. Shortly, CircMELK promotes chondrocyte apoptosis and inhibits autophagy in OA by regulating MYD88/NF-kappaB signaling axis through miR-497-5p. Our study proposes a new molecular mechanism for the development of OA. CI - Copyright (c) 2022 Yingchi Zhang et al. FAU - Zhang, Yingchi AU - Zhang Y AUID- ORCID: 0000-0002-3892-2946 AD - Department of Traumatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. FAU - Lu, Rui AU - Lu R AUID- ORCID: 0000-0002-4909-4007 AD - Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. FAU - Huang, Xiaojian AU - Huang X AUID- ORCID: 0000-0003-0047-6343 AD - Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. FAU - Yin, Enzhi AU - Yin E AD - Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. FAU - Yang, Yong AU - Yang Y AD - Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. FAU - Yi, Chengla AU - Yi C AUID- ORCID: 0000-0003-2585-3571 AD - Department of Traumatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. FAU - You, Hongbo AU - You H AUID- ORCID: 0000-0001-6284-643X AD - Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. FAU - Song, Xianzhou AU - Song X AD - Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. FAU - Yuan, Xuefeng AU - Yuan X AUID- ORCID: 0000-0002-6620-7528 AD - Department of Traumatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220730 PL - England TA - Contrast Media Mol Imaging JT - Contrast media & molecular imaging JID - 101286760 RN - 0 (MIRN497 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (RNA, Circular) RN - EC 2.7.1.- (MELK protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Apoptosis/genetics/physiology MH - Autophagy/genetics/physiology MH - Chondrocytes/metabolism MH - Humans MH - Inflammation/genetics/metabolism MH - *MicroRNAs/genetics/metabolism MH - *Myeloid Differentiation Factor 88/genetics/metabolism MH - *NF-kappa B/genetics/metabolism MH - *Osteoarthritis/genetics/metabolism/pathology MH - *Protein Serine-Threonine Kinases/genetics/metabolism MH - *RNA, Circular/genetics/metabolism PMC - PMC9356867 COIS- The authors declare that they have no conflicts of interest. EDAT- 2022/08/23 06:00 MHDA- 2022/08/24 06:00 PMCR- 2022/07/30 CRDT- 2022/08/22 04:29 PHST- 2022/05/09 00:00 [received] PHST- 2022/06/09 00:00 [revised] PHST- 2022/06/15 00:00 [accepted] PHST- 2022/08/22 04:29 [entrez] PHST- 2022/08/23 06:00 [pubmed] PHST- 2022/08/24 06:00 [medline] PHST- 2022/07/30 00:00 [pmc-release] AID - 10.1155/2022/7614497 [doi] PST - epublish SO - Contrast Media Mol Imaging. 2022 Jul 30;2022:7614497. doi: 10.1155/2022/7614497. eCollection 2022.