Lubricin/proteoglycan 4 increases in both experimental and naturally occurring equine osteoarthritis

Abstract

SUMMARY Objective The goals of this study were (1) to quantify proteoglycan 4 (PRG4) gene expression; (2) to assess lubricin immunostaining; and (3) to measure synovial fluid lubricin concentrations in clinical and experimental models of equine carpal osteoarthritis (OA). Design Lubricin synovial fluid concentrations and cartilage and synovial membrane PRG4 expression were analyzed in research horses undergoing experimental OA induction (n = 8) and in equine clinical patients with carpal OA (n = 58). Lubricin concentrations were measured using a custom sandwich enzyme-linked immunosorbent assay, and PRG4 expression was quantified using qRT-PCR. Lubricin immunostaining was assessed in synovial membrane and osteochondral sections in the experimental model. Results Lubricin concentrations increased in synovial fluid following induction of OA, peaking at 21 days post-operatively in OA joints vs sham-operated controls (331 ± 69 μg/mL vs 110 ± 19 μg/mL, P = 0.001). Lubricin concentrations also increased in horses with naturally occurring OA as compared to control joints (152 ± 32 μg/mL vs 68 ± 4 μg/mL, P = 0.003). Synovial membrane PRG4 expression increased nearly 2-fold in naturally occurring OA (P = 0.003), whereas cartilage PRG4 expression decreased 2.5-fold (P = 0.025). Lubricin immunostaining was more pronounced in synovial membrane from OA joints as compared to controls, with intense lubricin localization to sites of cartilage damage. Conclusions Although PRG4 gene expression decreases in OA cartilage, synovial membrane PRG4 expression, synovial fluid lubricin concentrations and lubricin immunostaining all increase in an equine OA model. Lubricin may be elevated to protect joints from post-traumatic OA.

Two compartment pharmacokinetic model describes the intra‐articular delivery and retention of rhprg4 following ACL transection in the Yucatan mini pig

“…By contrast, 5 days after surgery also likely diminished resident porcine PRG4 levels . However, an increase in native PRG4 expression from the synovium as observed in an equine OA model, 20 days following surgery has not been excluded. Our study was conducted cumulatively across three groups of animals due to logistical challenges.…”

Galectins-1 and-3 Increase in Equine Post-traumatic Osteoarthritis

“…Galectin-1 synovial fluid concentrations were most elevated acutely after injury, whereas elevations in galectin-3 were sustained up to the end of the study duration (day 75) in one cohort of horses (Figure 1D ). Galectin-3 was moderately correlated with synovial fluid lubricin (ρ = 0.47, P < 0.0001), whereas galectin-1 was weakly correlated with lubricin (ρ = 0.27, P = 0.007) ( 32 ). Galectin-1 and-3 synovial fluid levels were weakly correlated (ρ = 0.31, P = 0.002).…”

“…Synovial membrane biopsies and osteochondral tissues were collected from the first cohort ( n = 5) for immunohistochemistry following euthanasia on day 70 post-fragmentation. Analysis of synovial fluid lubricin concentrations and lubricin immunostaining has previously been reported in the first cohort ( 32 ). Horses in both cohorts were subjected to carpal osteochondral fragmentation in one randomly assigned joint, while the opposite joint served as a sham-operated control.…”

“…Model diagnostics were performed and showed normality and homoscedasticity of residuals. Spearman correlation analysis was performed to determine associations between synovial fluid galectin-1 and galectin-3 levels and previously published lubricin ELISA data for the first experimental cohort and for the naturally occurring OA cases ( 32 ). Raw RT-qPCR and ELISA data from naturally occurring samples were log-transformed to achieve normality of the data, and data were analyzed using a one-way ANOVA with Dunnett's post hoc tests for multiple comparison correction, designating healthy carpal joints (OA severity = 0) as the control group.…”

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“…SVALA et al, 2015), principalmente nos locais mais danificados, caracterizados pela presença de fissuras, fibrilações e perda de proteoglicanos.Ainda, a lubricina foi encontrada nos tecidos cicatriciais, sugerindo ser um importante mediador no reparo e cicatrização cartilagíneos(REESINK et al, 2017). O LS contém, ainda, moléculas solúveis como citocinas e fatores de crescimento, que além de permitirem a comunicação entre as diferentes populações celulares da articulação, como condrócitos e células sinoviais, também atuam como fatores regulatórios para as mesmas(BLEWIS et al, 2010).…”