title: Full-Length Recombinant Human Proteoglycan 4 Interacts with Hyaluronan to Provide Cartilage Boundary Lubrication.
abstract: Proteoglycan 4 (PRG4) is a mucin-like glycoprotein present in synovial fluid and at the surface of articular cartilage. The objectives of this study were to (1) assess the articular cartilage surface adsorption and in vitro cartilage boundary lubricating ability of full-length recombinant human PRG4 (rhPRG4), and (2) cartilage boundary lubricating ability of purified rhPRG4, both alone and in combination with hyaluronan (HA). rhPRG4 adsorption onto articular cartilage explants was assessed by immunohistochemistry and dot blot. An in vitro cartilage-cartilage friction test was used to assess rhPRG4's cartilage boundary lubricating ability compared to bovine PRG4, and that of purified rhPRG4 both alone and in combination with HA. rhPRG4 was able to adsorb to the articular surface, as well as the cut surface, of cartilage explants. The kinetic coefficient of friction of rhPRG4 was similar to that of PRG4 (p = 0.16) and lower than phosphate-buffered saline (p < 0.05), while that of purified rhPRG4 + HA was significantly lower than rhPRG4 alone (p < 0.05). This study demonstrates that rhPRG4 can adsorb to an intact articular cartilage surface and functions as an effective boundary lubricant, both alone and with HA, and provides the foundation for in vivo evaluation of this clinically relevant full-length rhPRG4 for treatment of osteoarthritis.
authors.affiliation: Biomedical Engineering Graduate Program, University of Calgary, 2500 University Dr NW, KNB 426, Calgary, AB, T2N 1N4, Canada.|McCaig Institute of Bone and Joint Health, University of Calgary, Calgary, AB, Canada.
authors.forename: Saleem
authors.initials: S
authors.lastname: Abubacker
authors.affiliation: Biomedical Engineering Graduate Program, University of Calgary, 2500 University Dr NW, KNB 426, Calgary, AB, T2N 1N4, Canada.|McCaig Institute of Bone and Joint Health, University of Calgary, Calgary, AB, Canada.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Dorosz
authors.affiliation: McCaig Institute of Bone and Joint Health, University of Calgary, Calgary, AB, Canada.|Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Dragana
authors.initials: D
authors.lastname: Ponjevic
authors.affiliation: Center for Biomedical Engineering and the School of Engineering, Brown University, Providence, RI, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Jay
authors.affiliation: McCaig Institute of Bone and Joint Health, University of Calgary, Calgary, AB, Canada.|Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: Matyas
authors.affiliation: Biomedical Engineering Graduate Program, University of Calgary, 2500 University Dr NW, KNB 426, Calgary, AB, T2N 1N4, Canada. tschmidt@ucalgary.ca.|McCaig Institute of Bone and Joint Health, University of Calgary, Calgary, AB, Canada. tschmidt@ucalgary.ca.|Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada. tschmidt@ucalgary.ca.
authors.forename: Tannin A
authors.initials: TA
authors.lastname: Schmidt
mesh_terms: D000327:Adsorption; D000818:Animals; D016466:CHO Cells; D002358:Cartilage, Articular / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D003412:Cricetulus; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013264:Stifle / Q000737:chemistry / Q000378:metabolism; D000099158:Proteoglycan 4
chemical_list: D006820:Hyaluronic Acid; D011509:Proteoglycans; D011994:Recombinant Proteins; C419197:PRG4 protein, human; D000099158:Proteoglycan 4
keywords: Cartilage boundary lubrication; Hyaluronan (HA); Osteoarthritis (OA); Proteoglycan 4 (PRG4)