Binding and localization of recombinant lubricin to articular cartilage surfaces

Jones, Ann Rosalind; Gleghorn, Jason P.; Hughes, Claire E.; Fitz, Lori; Zollner, Richard; Wainwright, S.D.; Caterson, Bruce; Morris, Elizabeth A.; Bonassar, Lawrence J.; Flannery, Carl R.

doi:10.1002/jor.20325

Cited by 136 publications

(178 citation statements)

References 42 publications

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“…Concentrations of TGF-b1 and IL-1b were chosen based on previous changes in SZP protein expression in culture. 19,20 A decrease in SZP protein expression has been observed for IL-1a treatment of articular cartilage 7,21,22 and for IL-1b in mandibular condyle chondrocytes 23 at similar concentrations.…”

Section: Tissue Acquisition and Culturementioning

confidence: 77%

Regulation of the friction coefficient of articular cartilage by TGF‐β1 and IL‐1β

DuRaine

Neu

Chan

et al. 2008

Journal Orthopaedic Research

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Articular cartilage functions to provide a low-friction surface for joint movement for many decades of life. Superficial zone protein (SZP) is a glycoprotein secreted by chondrocytes in the superficial layer of articular cartilage that contributes to effective boundary lubrication. In both cell and explant cultures, TGF-b1 and IL-1b have been demonstrated to, respectively, upregulate and downregulate SZP protein levels. It was hypothesized that the friction coefficient of articular cartilage could also be modulated by these cytokines through SZP regulation. The friction coefficient between cartilage explants (both untreated and treated with TGF-b1 or IL-1b) and a smooth glass surface due to sliding in the boundary lubrication regime was measured with a pin-on-disk tribometer. SZP was quantified using an enzyme-linked immunosorbant assay and localized by immunohistochemistry. Both TGF-b1 and IL-1b treatments resulted in the decrease of the friction coefficient of articular cartilage in a location-and time-dependent manner. Changes in the friction coefficient due to the TGF-b1 treatment corresponded to increased depth of SZP staining within the superficial zone, while friction coefficient changes due to the IL-1b treatment were independent of SZP depth of staining. However, the changes induced by the IL-1b treatment corresponded to changes in surface roughness, determined from the analysis of surface images obtained with an atomic force microscope. These findings demonstrate that the low friction of articular cartilage can be modified by TGF-b1 and IL-1b treatment and that the friction coefficient depends on multiple factors, including SZP localization and surface roughness. ß

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Section: Tissue Acquisition and Culturementioning

confidence: 77%

Regulation of the friction coefficient of articular cartilage by TGF‐β1 and IL‐1β

DuRaine

Neu

Chan

et al. 2008

Journal Orthopaedic Research

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“…This is, however, in contrast to recent findings where 1.5M NaCl was sufficient to remove PRG4 from the articular surface of immature bovine cartilage disks. 29 This discrepancy could be due to differences in the strength with which PRG4 is held at the surfaces of immature and adult tissue.…”

Section: Discussionmentioning

confidence: 99%

PRG4 exchange between the articular cartilage surface and synovial fluid

Nugent-Derfus

Chan

Schumacher

et al. 2007

Journal Orthopaedic Research

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ABSTRACT:The boundary lubrication function of articular cartilage is mediated in part by proteoglycan 4 (PRG4) molecules, found both in synovial fluid (SF) and bound to the articular cartilage surface. Currently the mechanism by which PRG4 binds to the articular surface is not well understood. The objectives of this study were to determine (1) the effect of bathing fluid contents on PRG4 concentration at the articular surface ([PRG4] cart ), and (2) whether native PRG4 can be removed from the surface and subsequently repleted with PRG4 from synovial fluid. In one experiment, cylindrical cartilage disks were stored in solutions of various PRG4 concentrations, either in phosphate-buffered saline (PBS) or SF as the carrier fluid. In a separate experiment, cartilage disks were stored in solutions expected to remove native PRG4 from the articular surface and allow subsequent repletion with PRG4 from SF. [PRG4] cart was independent of PRG4 concentration of the bathing fluid, and was similar for both carrier fluids. PRG4 was removed from cartilage by treatment with hyaluronidase, reduction/alkylation, and sodium dodecyl sulphate, and was repleted fully by subsequent bathing in SF. These results suggest that the articular surface is normally saturated with tightly bound PRG4, but this PRG4 can exchange with the PRG4 in SF under certain conditions. This finding suggests that all tissues surrounding the joint cavity that secrete PRG4 into the SF may help to maintain lubrication function at the articular surface. ß

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“…Authors: This proportion can be estimated as follows. The amount of PRG4 bound to the surface of bovine cartilage is ~0.24-0.59 µg/cm 2 Nugent et al, 2006). Using parameter values from the present manuscript, a joint with 140 cm 2 cartilage surface area (Eckstein et al, 2001) would have a total of ~34-83 µg bound PRG4.…”

mentioning

confidence: 83%

A model of synovial fluid lubricant composition in normal and injured joints

Blewis

Nugent-Derfus²,

Schmidt³

et al. 2007

eCM

126

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The synovial fluid (SF) of joints normally functions as a biological lubricant, providing low-friction and low-wear properties to articulating cartilage surfaces through the putative contributions of proteoglycan 4 (PRG4), hyaluronic acid (HA), and surface active phospholipids (SAPL). These lubricants are secreted by chondrocytes in articular cartilage and synoviocytes in synovium, and concentrated in the synovial space by the semi-permeable synovial lining. A deficiency in this lubricating system may contribute to the erosion of articulating cartilage surfaces in conditions of arthritis. A quantitative intercompartmental model was developed to predict in vivo SF lubricant concentration in the human knee joint. The model consists of a SF compartment that (a) is lined by cells of appropriate types, (b) is bound by a semi-permeable membrane, and (c) contains factors that regulate lubricant secretion. Lubricant concentration was predicted with different chemical regulators of chondrocyte and synoviocyte secretion, and also with therapeutic interventions of joint lavage and HA injection. The model predicted steady-state lubricant concentrations that were within physiologically observed ranges, and which were markedly altered with chemical regulation. The model also predicted that when starting from a zero lubricant concentration after joint lavage, PRG4 reaches steady-state concentration ~10-40 times faster than HA. Additionally, analysis of the clearance rate of HA after therapeutic injection into SF predicted that the majority of HA leaves the joint after ~1-2 days. This quantitative intercompartmental model allows integration of biophysical processes to identify both environmental factors and clinical therapies that affect SF lubricant composition in whole joints.

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Binding and localization of recombinant lubricin to articular cartilage surfaces

Cited by 136 publications

References 42 publications

Regulation of the friction coefficient of articular cartilage by TGF‐β1 and IL‐1β

Regulation of the friction coefficient of articular cartilage by TGF‐β1 and IL‐1β

PRG4 exchange between the articular cartilage surface and synovial fluid

A model of synovial fluid lubricant composition in normal and injured joints

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