2015
DOI: 10.1186/s13075-015-0877-x
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The interaction of lubricin/proteoglycan 4 (PRG4) with toll-like receptors 2 and 4: an anti-inflammatory role of PRG4 in synovial fluid

Abstract: BackgroundLubricin/proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. PRG4 has a homeostatic multifaceted role in the joint. PRG4 intra-articular treatment retards progression of cartilage degeneration in pre-clinical posttraumatic osteoarthritis models. The objective of this study is to evaluate the binding of recombinant human PRG4 (rhPRG4) and native human PRG4 (nhPRG4) to toll-like receptors 2 and 4 (TLR2 and TLR4) and whether this interacti… Show more

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Cited by 112 publications
(118 citation statements)
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“…While PRG4 has been commonly thought of as a bio‐lubricant, a number of additional biological roles have been described. PRG4 directly binds to toll‐like receptors (TLRs) and regulates the inflammatory response both in vitro and in vivo . We therefore chose to examine two common OA treatments, that each partially recapitulate a biomechanical or anti‐inflammatory role of PRG4; HA, which can provide hydrodynamic lubrication to the joint and corticosteroids which regulate inflammation.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…While PRG4 has been commonly thought of as a bio‐lubricant, a number of additional biological roles have been described. PRG4 directly binds to toll‐like receptors (TLRs) and regulates the inflammatory response both in vitro and in vivo . We therefore chose to examine two common OA treatments, that each partially recapitulate a biomechanical or anti‐inflammatory role of PRG4; HA, which can provide hydrodynamic lubrication to the joint and corticosteroids which regulate inflammation.…”
Section: Resultsmentioning
confidence: 99%
“…PRG4 directly binds to toll-like receptors (TLRs) and regulates the inflammatory response both in vitro and in vivo. 27,31 We therefore chose to examine two common OA treatments, that each partially recapitulate a biomechanical or anti-inflammatory role of PRG4; HA, which can provide hydrodynamic lubrication to the joint and corticosteroids which regulate inflammation. Inclusion of these treatment groups in addition to a direct rescue through administration of rhPRG4 allowed us to determine if regulation of lubrication and/or inflammation impacted the subchondral bone in C57BL/6 and Prg4 −/− mice.…”
Section: Longitudinal Repeated Measures Analysis Of Prg4 −/− Bone Mormentioning
confidence: 99%
“…Originally perceived solely as a lubricating molecule in these diverse tissues, we suggest that in addition to reducing friction between biological surfaces a growing body of literature suggests that PRG4 has the ability to interact with immune cells. This implies that PRG4 may play key roles in immunity and/or the regulation of the inflammatory response . In this manuscript, we introduce known lubrication functions of PRG4 and present a hypothesis supported by the literature that PRG4 acts a buffer in the inflammatory response.…”
Section: Introductionmentioning
confidence: 81%
“…These findings suggest that lubricin, in addition to enhancing lubrication, may possess anti-inflammatory functions distinct from its lubricating properties in joint trauma. Recently, lubricin has been shown to inhibit synovial inflammation via binding to both the CD44 receptor 42 and Toll-like receptors 2 and 4 43,44 .…”
Section: Discussionmentioning
confidence: 99%