{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T03:01:59Z","timestamp":1776308519725,"version":"3.50.1"},"reference-count":87,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:00:00Z","timestamp":1649721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR067748"],"award-info":[{"award-number":["R01AR067748"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4\u2014PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene Prg4 served as a model that recapitulates the destructive arthrosis that involves biofouling of cartilage by serum proteins in lieu of Prg4. This study hypothesized that Prg4-deficient mice would demonstrate a quadruped gait change and decreased markers of mitochondrial dyscrasia, following intra-articular injection of both hindlimbs with recombinant human PRG4 (rhPRG4). Prg4\u2212\/\u2212 (N = 44) mice of both sexes were injected with rhPRG4 and gait alterations were studied at post-injection day 3 and 6, before joints were harvested for immunohistochemistry for caspase-3 activation. Increased stance and propulsion was shown at 3 days post-injection in male mice. There were significantly fewer caspase-3-positive chondrocytes in tibiofemoral cartilage from rhPRG4-injected mice. The mitochondrial gene Mt-tn, and myosin heavy (Myh7) and light chains (Myl2 and Myl3), known to play a cytoskeletal stabilizing role, were significantly upregulated in both sexes (RNA-Seq) following IA rhPRG4. Chondrocyte mitochondrial dyscrasias attributable to the arthrosis in CACP may be mitigated by IA rhPRG4. In a supporting in vitro crystal microbalance experiment, molecular fouling by albumin did not block the surface activity of rhPRG4.<\/jats:p>","DOI":"10.3390\/ijms23084245","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T02:48:59Z","timestamp":1649731739000},"page":"4245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Quadruped Gait and Regulation of Apoptotic Factors in Tibiofemoral Joints following Intra-Articular rhPRG4 Injection in Prg4 Null Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Daniel S.","family":"Yang","sequence":"first","affiliation":[{"name":"School of Engineering, Brown University, Providence, RI 02912, USA"},{"name":"Department of Emergency Medicine, Alpert School of Medicine, Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward E.","family":"Dickerson","sequence":"additional","affiliation":[{"name":"North Carolina Agricultural Technical State University, Greensboro, NC 27411, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling X.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Alpert School of Medicine, Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"Richendrfer","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Alpert School of Medicine, Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Padmini N.","family":"Karamchedu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Alpert School of Medicine, Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary J.","family":"Badger","sequence":"additional","affiliation":[{"name":"Department of Medical Biostatistics, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7140-254X","authenticated-orcid":false,"given":"Tannin A.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Dental Medicine, University of Connecticut Health, Farmington, CT 06030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alger M.","family":"Fredericks","sequence":"additional","affiliation":[{"name":"Department of Surgery, Alpert School of Medicine, Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8925-4255","authenticated-orcid":false,"given":"Khaled A.","family":"Elsaid","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chapman University, Irvine, CA 92618, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1517-8488","authenticated-orcid":false,"given":"Gregory D.","family":"Jay","sequence":"additional","affiliation":[{"name":"School of Engineering, Brown University, Providence, RI 02912, USA"},{"name":"Department of Emergency Medicine, Alpert School of Medicine, Brown University, Providence, RI 02903, USA"},{"name":"Department of Orthopedics, Alpert School of Medicine, Brown University, Providence, RI 02903, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,12]]},"reference":[{"key":"ref_1","first-page":"503","article-title":"Lubricin reduces cartilage\u2014Cartilage integration","volume":"41","author":"Schaefer","year":"2004","journal-title":"Biorheology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31325","DOI":"10.1074\/jbc.M505401200","article-title":"Consequences of Disease-causing Mutations on Lubricin Protein Synthesis, Secretion, and Post-translational Processing","volume":"280","author":"Rhee","year":"2005","journal-title":"J. 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