Temporal changes in synovial fluid composition and elastoviscous lubrication in the equine carpal fracture model

Abstract

The objective of this study was to examine temporal variations in synovial fluid composition and lubrication following articular fracture. Post-traumatic osteoarthritis (PTOA) was induced by creating an osteochondral fracture in the middle carpal joint of four horses while the contralateral limb served as a sham-operated control. Horses were exercised on a high-speed treadmill, and synovial fluid was collected pre-operatively and at serial timepoints until 75 days post-operatively. Lubricin and hyaluronic acid (HA) concentrations were measured using sandwich ELISAs, and the molecular weight distribution of HA was analyzed via gel electrophoresis. Synovial fluid viscosity and cartilage friction coefficients across all modes of lubrication were measured on days 0, 19, 33, and 61 using a commercial rheometer and a custom tribometer, respectively. HA concentrations were significantly decreased post-operatively, and high molecular weight HA (>6.1MDa) did not recover to pre-operative values by the study termination at day 75. Lubricin concentrations increased after surgery to a greater extent in the OA as compared to sham-operated limbs. Viscosity was significantly reduced after surgery. While boundary and elastoviscous mode friction coefficients did not vary, the transition number, representing the shift between these modes, was lower. Although more pronounced in the OA limbs, similar derangements in HA, HA molecular weight distribution, viscosity, and transition number were observed in the sham-operated limbs, which may be explained by synovial fluid washout during arthroscopy. ß

Synovial fluid lubricin increases in spontaneous canine cruciate ligament rupture

“…As compared to rodent and rabbit models, synovial fluid acquisition is more reliable in large animal models such as the dog, sheep, and horse, where synovial fluid can be directly aspirated without the requirement for joint lavage. Interestingly, elevated synovial fluid lubricin has been observed in both experimental and naturally occurring PTOA in horses [19][20][21][22]39 , similar to that observed in spontaneous canine RCCL in the current study.…”

“…However, elevated synovial fluid lubricin concentrations have been reported in humans with tibial plateau fracture and late-stage OA 17,18 . Similar increases in synovial fluid lubricin have also been observed in several studies in both experimentally-induced and naturally occurring PTOA models in horses [19][20][21][22] . However, studies evaluating synovial fluid lubricin in other large animal models, especially large animal models of knee joint instability, are lacking.…”

Investigation of Synovial Fluid Lubricants and Inflammatory Cytokines in the Horse: a Comparison of Recombinant Equine Interleukin 1β-induced Synovitis and Joint Lavage Models

“…[39][40][41] Interestingly, in prior studies investigating the equine carpal osteochondral fragment high-speed treadmill exercise model, synovial uid lubricin concentrations were increased in both the fracture joint and, to a lesser extent, in the sham-operated control joint, possibly due to compensatory overloading of the control limb. 11,40 Results from the current study may be able to help account for the ndings in the shamoperated control joint, as these carpi undergo lavage during the arthroscopic sham-operation and are subjected to repeated arthrocentesis at weekly or more frequent intervals. LPS-induced equine synovitis models have shown decreased HA over a 48-hour period, and a quantitative intercompartmental synovial joint model predicted that HA would take longer to reach a steady state concentration than lubricin following intra-articular lavage.…”

“…10 Following arthroscopy of equine middle carpal joints, synovial uid viscosities and HA concentrations decrease for up to 75 days. 11 Bovine cartilage explants, lubricated with lubricin-de cient synovial uid from humans with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), reveal increased friction coe cients and increased chondrocyte apoptosis as compared to normal synovial uid or CACP synovial uid to which lubricin has been added. 12 These changes lead to cartilage degradation and perpetuation of in ammation, highlighting the importance of lubricin's cartilage lubricating function.…”

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

“…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).…”