{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:58:25Z","timestamp":1792123105636,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2017,6,11]],"date-time":"2017-06-11T00:00:00Z","timestamp":1497139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Deficiency of PRG4 (lubricin), the boundary lubricant in mammalian joints, contributes to increased joint friction accompanied by superficial and upper intermediate zone chondrocyte caspase-3 activation, as shown in lubricin-null (Prg4\u2212\/\u2212) mice. Caspase-3 activity appears to be reversible upon the restitution of Prg4 either endogenously in vivo, in a gene trap mouse, or as an applied lubricant in vitro. In this study we show that intra-articular injection of human PRG4 in vivo in Prg4\u2212\/\u2212 mice prevented caspase-3 activation in superficial zone chondrocytes and was associated with a modest decrease in whole joint friction measured ex vivo using a joint pendulum method. Non-lubricated Prg4\u2212\/\u2212 mouse cartilage shows caspase cascade activation caused by mitochondrial dysregulation, and significantly higher levels of peroxynitrite (ONOO\u2212 and \u2212OH) and superoxide (O\u22122) compared to Prg4+\/+ and Prg4+\/\u2212 cartilage. Enzymatic activity levels of caspase 8 across Prg4 mutant mice were not significantly different, indicating no extrinsic apoptosis pathway activation. Western blots showed caspase-3 and 9 activation in Prg4\u2212\/\u2212 tissue extracts, and the appearance of nitrosylated Cys163 in the active cleft of caspase-3 which inhibits its enzymatic activity. These findings are relevant to patients at risk for arthrosis, from camptodactyl-arthropathy-coxa vara-pericarditis (CACP) syndrome and transient lubricin insufficiency due to trauma and inflammation.<\/jats:p>","DOI":"10.3390\/ijms18061252","type":"journal-article","created":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T10:27:59Z","timestamp":1497263279000},"page":"1252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Friction-Induced Mitochondrial Dysregulation Contributes to Joint Deterioration in Prg4 Knockout Mice"],"prefix":"10.3390","volume":"18","author":[{"given":"Kimberly","family":"Waller","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Warren Alpert School of Medicine and Rhode Island Hospital, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Warren Alpert School of Medicine and Rhode Island Hospital, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1517-8488","authenticated-orcid":false,"given":"Gregory","family":"Jay","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Warren Alpert School of Medicine and Rhode Island Hospital, Providence, RI 02903, USA"},{"name":"School of Engineering, Brown University, Providence, RI 02912, USA"},{"name":"Department of Emergency Medicine, Rhode Island Hospital, Coro West, 1 Hoppin Street, Suite 106, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.1002\/art.39276","article-title":"Lubricin restoration in a mouse model of congenital deficiency","volume":"67","author":"Hill","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/15496","article-title":"CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome","volume":"23","author":"Marcelino","year":"1999","journal-title":"Nat. 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