title: Reduction of friction by recombinant human proteoglycan 4 in IL-1α stimulated bovine cartilage explants.
abstract: A boundary lubricant attaches and protects sliding bearing surfaces by preventing interlocking asperity-asperity contact. Proteoglycan-4 (PRG4) is a boundary lubricant found in the synovial fluid that provides chondroprotection to articular surfaces. Inflammation of the diarthrodial joint modulates local PRG4 concentration. Thus, we measured the effects of inflammation, with Interleukin-1α (IL-1α) incubation, upon boundary lubrication and PRG4 expression in bovine cartilage explants. We further aimed to determine whether the addition of exogenous human recombinant PRG4 (rhPRG4) could mitigate the effects of inflammation on boundary lubrication and PRG4 expression in vitro. Cartilage explants, following a 7 day incubation with IL-1α, were tested in a disc-on-disc configuration using either rhPRG4 or saline (PBS control) as a lubricant. Following mechanical testing, explants were studied immunohistochemically or underwent RNA extraction for real-time polymerase chain reaction (RT-PCR). We found that static coefficient of friction (COF) significantly decreased to 0.14 ± 0.065 from 0.21 ± 0.059 (p = 0.014) in IL-1α stimulated explants lubricated with rhPRG4, as compared to PBS. PRG4 expression was significantly up regulated from 30.8 ± 19 copies in control explants lubricated with PBS to 3330 ± 1760 copies in control explants lubricated with rhPRG4 (p < 0.001). Explants stimulated with IL-1α displayed no increase in PRG4 expression upon lubrication with rhPRG4, but with PBS as the lubricant, IL-1α stimulation significantly increased PRG4 expression compared to the control condition from 30.8 ± 19 copies to 401 ± 340 copies (p = 0.015). Overall, these data suggest that exogenous rhPRG4 may provide a therapeutic option for reducing friction in transient inflammatory conditions and increasing PRG4 expression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:580-589, 2017.
authors.affiliation: Center for Biomedical Engineering and School of Engineering, Brown University, Providence, Rhode Island.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Larson
authors.affiliation: Emergency Medicine Research Laboratory, Department of Emergency Medicine, Rhode Island Hospital, Providence, Rhode Island.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, California.
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Elsaid
authors.affiliation: Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.|Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Tannin A
authors.initials: TA
authors.lastname: Schmidt
authors.affiliation: Center for Biomedical Engineering and School of Engineering, Brown University, Providence, Rhode Island.|Bioengineering Laboratory, Department of Orthopaedics, Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, Rhode Island.
authors.forename: Braden C
authors.initials: BC
authors.lastname: Fleming
authors.affiliation: Department of Medical Biostatistics, University of Vermont, Burlington, Vermont.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Badger
authors.affiliation: Center for Biomedical Engineering and School of Engineering, Brown University, Providence, Rhode Island.|Emergency Medicine Research Laboratory, Department of Emergency Medicine, Rhode Island Hospital, Providence, Rhode Island.|Department of Emergency Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Jay
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects*; D002417:Cattle; D004353:Drug Evaluation, Preclinical; D017276:Friction / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D053582:Interleukin-1alpha; D010003:Osteoarthritis / Q000188:drug therapy*; D011509:Proteoglycans / Q000627:therapeutic use*; D000099158:Proteoglycan 4
chemical_list: D053582:Interleukin-1alpha; D011509:Proteoglycans; C419197:PRG4 protein, human; D000099158:Proteoglycan 4
keywords: Interleukin-1; PRG4; articular cartilage; biomechanics; lubricin; post-traumatic osteoarthritis; tribology, friction