PMID- 28343378 OWN - NLM STAT- MEDLINE DCOM- 20170505 LR - 20240204 IS - 0219-1032 (Electronic) IS - 1016-8478 (Print) IS - 1016-8478 (Linking) VI - 40 IP - 3 DP - 2017 Mar TI - Adipose-Derived Stem Cells Suppress Inflammation Induced by IL-1beta through Down-Regulation of P2X7R Mediated by miR-373 in Chondrocytes of Osteoarthritis. PG - 222-229 LID - 10.14348/molcells.2017.2314 [doi] AB - Adipose-derived stem cells (ADSCs) were previously considered to have an anti-inflammatory effect, and Interleukin-1beta (IL-1beta) was found to be a pro-inflammatory factor in chondrocytes, but the mechanism underlying ADSCs and IL-1beta is unclear. In this study, we investigate whether P2X7 receptor (P2X7R) signalling, regulated by microRNA 373 (miR-373), was involved in the ADSCs and IL-1beta mediated inflammation in osteoarthritis (OA). Chondrocytes were collected from 20 OA patients and 20 control participants, and ADSCs were collected from patients who had undergone abdominal surgery. The typical surface molecules of ASDCs were detected by flow cytometry. The level of nitric oxide (NO) was determined by Griess reagent. Concentrations of prostaglandin E2 (PGE2), interleukin 6 (IL-6), matrix metallopeptidase 3 (MMP-3) were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of IL-6, MMP-3, miR-373 and P2X7R were determined by real-time polymerase chain reaction (PCR), and Western blot was used to detect the protein expression of P2X7R. The typical potential characters of ADSCs were verified. In chondrocytes or OA tissues, the miR-373 expression level was decreased, but the P2X7R expression was increased. IL-1beta stimulation increased the level of inflammatory factors in OA chondrocytes, and ADSCs co-cultured with IL-1beta-stimulated chondrocytes decreased the inflammation. OA chondrocytes transfected with the miR-373 inhibitor increased the inflammation level. The miR-373 mimic suppressed the inflammation by targeting P2X7R and regulated its expression, while its effect was reversed by overexpression of P2X7R. IL-1beta induced inflammation in OA chondrocytes, while ADSCs seemed to inhibit the expression of P2X7R that was regulated by miR-373 and involved in the anti-inflammatory process in OA. FAU - Jin, Rilong AU - Jin R AD - Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medical Zhejiang University, Hangzhou, 310003 China. FAU - Shen, Miaoda AU - Shen M AD - Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medical Zhejiang University, Hangzhou, 310003 China. FAU - Yu, Liedao AU - Yu L AD - Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medical Zhejiang University, Hangzhou, 310003 China. FAU - Wang, Xuanwei AU - Wang X AD - Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medical Zhejiang University, Hangzhou, 310003 China. FAU - Lin, Xiangjin AU - Lin X AD - Department of Orthopedics Surgery, The First Affiliated Hospital, College of Medical Zhejiang University, Hangzhou, 310003 China. LA - eng PT - Journal Article DEP - 20170327 PL - United States TA - Mol Cells JT - Molecules and cells JID - 9610936 RN - 0 (IL6 protein, human) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (MIRN374 microRNA 374, human) RN - 0 (MicroRNAs) RN - 0 (P2RX7 protein, human) RN - 0 (Receptors, Purinergic P2X7) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Adipocytes/*cytology/metabolism MH - Cells, Cultured MH - Chondrocytes/*cytology/metabolism MH - Coculture Techniques MH - Dinoprostone/metabolism MH - Gene Expression Regulation MH - Humans MH - Interleukin-1beta/*pharmacology MH - Interleukin-6/genetics/metabolism MH - Matrix Metalloproteinase 3/genetics/metabolism MH - MicroRNAs/*genetics MH - Nitric Oxide/metabolism MH - Osteoarthritis/genetics/*immunology MH - Receptors, Purinergic P2X7/*genetics/metabolism MH - Signal Transduction MH - Stem Cells/cytology/*metabolism PMC - PMC5386960 OTO - NOTNLM OT - P2X7R OT - adipose-derived stem cells OT - chondrocytes OT - miR-373 OT - osteoarthritis EDAT- 2017/03/28 06:00 MHDA- 2017/05/06 06:00 PMCR- 2017/03/27 CRDT- 2017/03/28 06:00 PHST- 2016/12/26 00:00 [received] PHST- 2017/01/17 00:00 [revised] PHST- 2017/02/07 00:00 [accepted] PHST- 2017/03/28 06:00 [pubmed] PHST- 2017/05/06 06:00 [medline] PHST- 2017/03/28 06:00 [entrez] PHST- 2017/03/27 00:00 [pmc-release] AID - S1016-8478(23)00605-2 [pii] AID - molce-40-3-222 [pii] AID - 10.14348/molcells.2017.2314 [doi] PST - ppublish SO - Mol Cells. 2017 Mar;40(3):222-229. doi: 10.14348/molcells.2017.2314. Epub 2017 Mar 27.