Proteoglycan-4 and hyaluronan composition in synovial fluid and serum from clinical equine subjects: relationship to cartilage boundary lubrication and viscosity of synovial fluid

Matheson, Austyn; Regmi, Suresh C.; Martin-Alarcon, Leonardo; Jay, Gregory D.; Scott, W. M.; Schmidt, Tannin A.

doi:10.1080/03008207.2020.1751140

Cited by 8 publications

(5 citation statements)

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“…Superior biomarkers would be capable of detecting sensitive changes at the timepoints of joint disease where treatments are the most critical. In equine synovial joints, PRG4 increases with injury (26,29) and disease (27) with potentially unrelated effects to serum (25). In human patients, serum PRG4 was unchanged in cases of rheumatoid arthritis (35) (0.53 to 1.41 µg/mL, measured by ELISA) and advanced joint disease (39) (0.25 to 1 µg/mL, measured by commercial ELISA kit), whereas plasma PRG4 was associated with joint space narrowing, after adjusting for age and sex (40).…”

Section: Discussionmentioning

confidence: 99%

“…Equine serum full-length PRG4 reactivity to the monoclonal antibody (mAb) 9G3 (Millipore Sigma, Etobicoke, Canada) was confirmed by western blotting using 3-8% SDS-PAGE, as described previously (25,31). The apparent molecular weight of serum PRG4 is comparable to that of rhPRG4 of ∼460 kDa (31,32).…”

Section: Prg4 Western Blotmentioning

confidence: 99%

“…Serum PRG4 concentrations were determined by competitive ELISA, as described previously (25). Briefly, the ELISA included the use of mAb-9G3, rhPRG4 standards, and a pre-treatment of serum and rhPRG4 standard with Sialidase-A (33) (ProZyme) at 37 • C, overnight.…”

Section: Prg4 Competitive Enzyme-linked-immunosorbent-assay (Elisa)mentioning

confidence: 99%

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The Effect of Intense Exercise on Equine Serum Proteoglycan-4/Lubricin

et al. 2020

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Objective: Local biological and biomechanical-stimuli modulate proteoglycan-4 secretion within synovial joints. For the horse, changes to proteoglycan-4 concentration and function are notable in acute joint injury and osteoarthritis. Proteoglycan-4 (also known as Lubricin) is present in the blood, however the effect of exercise on equine serum levels is unknown. The overall objective of this study was, therefore, to investigate the effect of intense exercise on serum proteoglycan-4 in thoroughbred horses.Methods: Samples of blood were taken from thoroughbreds (n = 12) during a chuckwagon racing event (Alberta, Canada). The chuckwagon race is a sprint racing event where teams of horses pull a combined 1,325 lbs (601 kg) of wagon and driver around a 5/8th mile (1 km) of dirt track, racing at full gallop to the finish. Blood samples were collected 30-min before the race start, and several timepoints post-race: 5-min, 90-min, 3-h, 12-h, and 23-h. Proteoglycan-4 concentrations in serum were quantified by enzyme-linked-immunosorbent-assay using recombinant-human proteoglycan-4 standards and anti-proteoglycan-4 mAb 9G3. The molecular weight of immunoreactive proteoglycan-4 in serum was assessed by western blot.Results: Proteoglyan-4 in serum demonstrated the expected high MW immunoreactivity to mAb 9G3, consistent with that of full length PRG4. Serum proteoglycan-4 decreased five-minutes post-race from baseline concentration (0.815 ± 0.175 to 0.466 ± 0.090 μg/mL, μ ± SEM, p < 0.01).Conclusions: The concentration of serum proteoglycan-4 in horses decreased significantly five min post-exercise. A potential explanation for this finding could be increased proteoglycan-4 clearance from the circulation. Further investigations could extend to complete the detailed characterization of proteoglycan-4 structure and its potential function within the blood as it relates to joint health and exercise.

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Section: Discussionmentioning

confidence: 99%

Section: Prg4 Western Blotmentioning

confidence: 99%

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The Effect of Intense Exercise on Equine Serum Proteoglycan-4/Lubricin

et al. 2020

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“…Lubrication of degraded cartilage with chondroitinase ABC was shown to be restored through re-establishing lamina splendens with a bioinspired mucoadhesive biopolymer chitosan catechol [635]. Furthermore, different tribological characteristics of articular cartilages were found in different joints and on different sites, implying the importance of physiological loading and motion input into the joints [636], in alternated biomechanical environments [637] and in joint injuries [638]. The importance of the understanding the lubrication mechanism was clearly recognized for the future development of tissue engineered cartilage [639] and alternative replacement materials such as hydrogels [640].…”

Section: Natural Synovial Joints and Artificial Joint Replacementsmentioning

confidence: 99%

A review of advances in tribology in 2020–2021

Meng

et al. 2022

Friction

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Around 1,000 peer-reviewed papers were selected from 3,450 articles published during 2020–2021, and reviewed as the representative advances in tribology research worldwide. The survey highlights the development in lubrication, wear and surface engineering, biotribology, high temperature tribology, and computational tribology, providing a show window of the achievements of recent fundamental and application researches in the field of tribology.

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“…Likewise, PRG4 production is reduced with OA, highlighting the need to preserve both functional components of the synovial fluid. PRG4 works in a dose-dependent manner to lower friction within the joint [ 18 , 19 ]. PRG4 deficiency has been shown to diminish the lubricating ability of synovial fluid, while PRG4 supplementation has been shown to improve the boundary lubrication function of synovial fluid [ 9 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Endogenous production of hyaluronan, PRG4, and cytokines is sensitive to cyclic loading in synoviocytes

et al. 2022

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Synovial fluid is composed of hyaluronan and proteoglycan-4 (PRG4 or lubricin), which work synergistically to maintain joint lubrication. In diseases like osteoarthritis, hyaluronan and PRG4 concentrations can be altered, resulting in lowered synovial fluid viscosity, and pro-inflammatory cytokine concentrations within the synovial fluid increase. Synovial fibroblasts within the synovium are responsible for contributing to synovial fluid and can be targeted to improve endogenous production of hyaluronan and PRG4 and to alter the cytokine profile. We cyclically loaded SW982 synoviocytes to 0%, 5%, 10%, or 20% strain for three hours at 1 Hz. To assess the impact of substrate stiffness, we compared the 0% strain group to cells grown on tissue culture plastic. We measured the expression of hyaluronan turnover genes, hyaluronan localization within the cell layer, hyaluronan concentration, PRG4 concentration, and the cytokine profile within the media. Our results show that the addition of cyclic loading increased HAS3 expression, but not in a magnitude-dependent response. Hyaluronidase expression was impacted by strain magnitude, which is exemplified by the decrease in hyaluronan concentration due to cyclic loading. We also show that PRG4 concentration is increased at 5% strain, while higher strain magnitude decreases overall PRG4 concentration. Finally, 10% and 20% strain show a distinct, more pro-inflammatory cytokine profile when compared to the unloaded group. Multivariate analysis showed distinct separation between certain strain groups in being able to predict strain group, hyaluronan concentration, and PRG4 concentration from gene expression or cytokine concentration data, highlighting the complexity of the system. Overall, this study shows that cyclic loading can be used tool to modulate the endogenous production of hyaluronan, PRG4, and cytokines from synovial fibroblasts.

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Proteoglycan-4 and hyaluronan composition in synovial fluid and serum from clinical equine subjects: relationship to cartilage boundary lubrication and viscosity of synovial fluid

Cited by 8 publications

References 47 publications

The Effect of Intense Exercise on Equine Serum Proteoglycan-4/Lubricin

The Effect of Intense Exercise on Equine Serum Proteoglycan-4/Lubricin

A review of advances in tribology in 2020–2021

Endogenous production of hyaluronan, PRG4, and cytokines is sensitive to cyclic loading in synoviocytes

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