title: P2X4 promotes interleukin‑1β production in osteoarthritis via NLRP1.
abstract: Interleukin‑1β (IL‑1β) has a significant role in osteoarthritis (OA). The purinergic receptor, P2X4, has previously been implicated in IL‑1β secretion. The NLRP1 inflammasome mediates the production of IL‑1β in inflammatory disorders. However, it is unknown whether P2X4 modulates NLRP1‑mediated IL‑1β release. In the present study, the correlation between the P2X4 receptor and NLRP1 was investigated in OA fibroblast‑like synoviocytes (OAFLS). The expression of P2X4 and NLRP1 was detected in the OAFLS. The OAFLS were stimulated with P2X4 and the levels of IL‑1β and matrix metalloproteinases (MMPs) were measured. To determine whether P2X4 is involved in NLRP1‑triggered IL‑1β production, NLRP1 small interfering RNA (siRNA) was used. In the OAFLS, a markedly higher expression of P2X4 and NLRP1 was revealed compared with that in the normal FLS. OAFLS stimulated by P2X4 resulted in concentration‑dependent increases in the production of IL‑1β, MMP‑3 and MMP‑9. Furthermore, P2X4‑mediated IL‑1β production was attenuated by the NLRP1 siRNA. The results of the present study indicate that P2X4 induced IL‑1β, MMP‑3 and MMP‑9 production in the OAFLS. IL‑1β induced by P2X4 is mediated via NLRP1. P2X4/NLRP1 may be important in the pathogenesis of OA and may represent a novel therapeutic target.
authors.affiliation: Department of Orthopedic Surgery, The General Hospital of Jinan Military Command, Jinan, Shandong 250031, P.R. China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Fan
authors.forename: Xuechun
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Guo
authors.forename: Xuecheng
authors.initials: X
authors.lastname: Cao
authors.forename: Jinfang
authors.initials: J
authors.lastname: Cai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D000070576:NLR Proteins; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D058848:Receptors, Purinergic P2X4 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053583:Interleukin-1beta; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D058848:Receptors, Purinergic P2X4; D011994:Recombinant Proteins; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9