PRG4 exchange between the articular cartilage surface and synovial fluid

Nugent-Derfus, G.E.; Chan, Agnes S.; Schumacher, Barbara L.; Sah, Robert L.

doi:10.1002/jor.20431

Cited by 45 publications

(49 citation statements)

References 27 publications

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“…As the HA is digested, a fraction of the LUB at the cartilage surface may be liberated into the solution as noted in ref. 19. However, as noted earlier (see also footnote*), the surface was not rinsed: The LUB may therefore be assumed to be present at the cartilage surface, but appears to make little difference to the friction and wear properties measured.…”

Section: Methodsmentioning

confidence: 71%

“…Because the interfacial HA layers at the cartilage surface are cross-linked and complexed with molecules of LUB, digestion of this layer also removes LUB molecules from the cartilage surface † in addition to removing the bulk of HA from the surface, thus decreasing the molecular weight of HA chains in the remaining layer (19). In the first series of "step-load" experiments, described below, the surfaces were not rinsed with fresh PBS following digestion, leaving the HA fragments and associated LUB in the solution between the surfaces (there is no evidence that LUB itself is affected by hyaluronidase).…”

Section: Resultsmentioning

confidence: 99%

“…In the first series of "step-load" experiments, described below, the surfaces were not rinsed with fresh PBS following digestion, leaving the HA fragments and associated LUB in the solution between the surfaces (there is no evidence that LUB itself is affected by hyaluronidase). Given the physical nature of the HA-LUB bond, the high affinity of LUB to the cartilage surface (19), and the long time periods (approximately 45 min) over which the friction forces were measured after HA digestion, one may presume that any "liberated" LUB had sufficient time to find its way back and readsorb to the cartilage surface or become trapped between the two shearing surfaces. In the second series of "dynamic-loading" experiments, described below, the cartilage surfaces were rinsed with fresh PBS after HA digestion, thereby removing both HA and liberated LUB from the surface and the solution.…”

Section: Resultsmentioning

confidence: 99%

“…19). Also, strictly, it is not established that LUB is naturally liberated from the cartilage surface during HA digestion, only that it can be easily removed by rinsing or washing.…”

mentioning

confidence: 99%

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Adaptive mechanically controlled lubrication mechanism found in articular joints

Greene

Banquy²,

Lee³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

211

225

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Articular cartilage is a highly efficacious water-based tribological system that is optimized to provide low friction and wear protection at both low and high loads (pressures) and sliding velocities that must last over a lifetime. Although many different lubrication mechanisms have been proposed, it is becoming increasingly apparent that the tribological performance of cartilage cannot be attributed to a single mechanism acting alone but on the synergistic action of multiple "modes" of lubrication that are adapted to provide optimum lubrication as the normal loads, shear stresses, and rates change. Hyaluronic acid (HA) is abundant in cartilage and synovial fluid and widely thought to play a principal role in joint lubrication although this role remains unclear. HA is also known to complex readily with the glycoprotein lubricin (LUB) to form a cross-linked network that has also been shown to be critical to the wear prevention mechanism of joints. Friction experiments on porcine cartilage using the surface forces apparatus, and enzymatic digestion, reveal an "adaptive" role for an HA-LUB complex whereby, under compression, nominally free HA diffusing out of the cartilage becomes mechanically, i.e., physically, trapped at the interface by the increasingly constricted collagen pore network. The mechanically trapped HA-LUB complex now acts as an effective (chemically bound) "boundary lubricant"-reducing the friction force slightly but, more importantly, eliminating wear damage to the rubbing/shearing surfaces. This paper focuses on the contribution of HA in cartilage lubrication; however, the system as a whole requires both HA and LUB to function optimally under all conditions. arthritis | mechanical trapping | elastohydrodynamic lubrication | biointerface | biolubrication A rticular joints are almost completely sealed from their surroundings-by the synovial membrane around the joint and by cartilage and bone above and below the joint (1, 2). These barriers restrict rapid chemical transport into and out of joints, making it difficult to replace or repair damaged internal tissue or macromolecules, particularly those molecules that are covalently attached (bound) to the internal cartilage surfaces (1-3). Thus, it is no surprise that the major molecules involved in joint lubrication [lubricin and hyaluronic acid (HA)] are noncovalently bound and yet-to function as effective "boundary lubricants" that exhibit low friction and protect surfaces from wear-they need to act as if they are chemically bound to the surfaces.Hyaluronic acid has long been considered a potential boundary lubricant for cartilage (3-6), although numerous friction experiments have shown that solutions of free HA exhibit little lubrication activity (4, 5). However, surface forces apparatus (SFA) experiments (4) on chemically grafted and cross-linked HA layers demonstrated that such HA provide excellent wear protection for surfaces shearing at high pressures (200 atm), even though high friction coefficients (μ ¼ 0.15 − 0.3) were measured. These results...

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Section: Methodsmentioning

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…19). Also, strictly, it is not established that LUB is naturally liberated from the cartilage surface during HA digestion, only that it can be easily removed by rinsing or washing.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Adaptive mechanically controlled lubrication mechanism found in articular joints

Greene

Banquy²,

Lee³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

211

225

View full text Add to dashboard Cite

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“…Finally, the relationship between lubricin in SF and lubricin bound to the articular cartilage is not completely known. However, there is evidence that equilibrium may exist between SF and surface-associated lubricin (34).…”

Section: Effects Of Acl Injury On Sf Lubricin Concentrationsmentioning

confidence: 99%

Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury

Elsaid¹,

Fleming²,

Oksendahl³

et al. 2008

Arthritis & Rheumatism

226

244

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Results. SF lubricin concentrations were significantly (P < 0.001) reduced at an early stage following ACL injury when compared with those in the contralateral joint. Within 12 months, the lubricin concentration in the injured knee (slope ‫؍‬ 0.006, SE ‫؍‬ 0.00010, P < 0.001) approached that in the contralateral knee, which did not change with time (slope ‫؍‬ ؊0.0002, SE ‫؍‬ 0.00050, P ‫؍‬ 0.71). TNF␣ levels showed a significant negative relationship with log 2 lubricin levels. IL-1␤, TNF␣, IL-6, procathepsin B, and neutrophil elastase concentrations in SF from injured knees were greater in samples from recently injured knees compared with those that were chronically injured. There were no detectable cytokines or enzymes in the SF of contralateral joints. Concentrations of sGAG were significantly (P ‫؍‬ 0.0002) higher in the SF from injured knees compared with the contralateral joints.Conclusion. The decrease in SF lubricin concentrations following ACL injury may place the joint at an increased risk of wear-induced damage as a consequence of lack of boundary lubrication, potentially leading to secondary osteoarthritis. The decrease in SF lubricin was associated with an increase in levels of inflammatory cytokines.Lubricin (also known as superficial zone protein or PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone articular chondrocytes (1-3). Lubricin is partly responsible for the lubrication of apposed and pressurized cartilage surfaces (4). It provides essential chondroprotective properties to articular cartilage, as evidenced by lack of cartilage surface integrity and surface disruption in PRG4-knockout mice (5). Previously, we have demonstrated decreased synovial fluid (SF) lubricating properties, indicative of decreased SF lubricin concentrations, in patients diagnosed as having traumatic synovitis (6). Altered joint mechanics lead to decreased lubricin expression in the superficial layer and decreased lubricin coating of the surface of articular cartilage, as shown in a sheep meniscectomy model (7). Lubricin expression is down-regulated by proinflammatory cytokines (e.g., interleukin-1␤ [IL-1␤], tumor necrosis factor ␣ [TNF␣], and IL-6) (8-10). Moreover, lubricin has been shown to be proteolytically susceptible to the effects of cysteine

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Recent Progress in Cartilage Lubrication

2021

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Healthy articular cartilage, covering the ends of bones in major joints such as hips and knees, presents the most efficiently‐lubricated surface known in nature, with friction coefficients as low as 0.001 up to physiologically high pressures. Such low friction is indeed essential for its well‐being. It minimizes wear‐and‐tear and hence the cartilage degradation associated with osteoarthritis, the most common joint disease, and, by reducing shear stress on the mechanotransductive, cartilage‐embedded chondrocytes (the only cell type in the cartilage), it regulates their function to maintain homeostasis. Understanding the origins of such low friction of the articular cartilage, therefore, is of major importance in order to alleviate disease symptoms, and slow or even reverse its breakdown. This progress report considers the relation between frictional behavior and the cellular mechanical environment in the cartilage, then reviews the mechanism of lubrication in the joints, in particular focusing on boundary lubrication. Following recent advances based on hydration lubrication, a proposed synergy between different molecular components of the synovial joints, acting together in enabling the low friction, has been proposed. Additionally, recent development of natural and bio‐inspired lubricants is reviewed.

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PRG4 exchange between the articular cartilage surface and synovial fluid

Cited by 45 publications

References 27 publications

Adaptive mechanically controlled lubrication mechanism found in articular joints

Adaptive mechanically controlled lubrication mechanism found in articular joints

Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury

Recent Progress in Cartilage Lubrication

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