Synovial fluid lubricin and hyaluronan are altered in equine osteochondral fragmentation, cartilage impact injury, and full‐thickness cartilage defect models

Abstract

The objectives of this study were to evaluate temporal changes in lubricin, hyaluronan (HA), and HA molecular weight (MW) distributions in three distinct models of equine joint injury affecting the carpal (wrist), tarsal (ankle), and femoropatellar (knee) joints. To establish ranges for lubricin, HA, and HA MW distributions across multiple joints, we first evaluated clinically healthy, high‐motion equine joints. Synovial fluid was collected from high‐motion joints in horses without clinical signs of joint disease (n = 11 horses, 102 joints) and from research horses undergoing carpal osteochondral fragmentation (n = 8), talar cartilage impact injury (n = 7), and femoral trochlear ridge full‐thickness cartilage injury (n = 22) prior to and following arthroscopically induced joint injury. Lubricin and HA concentrations were measured via enzyme‐linked immunosorbent assays, and gel electrophoresis was performed to evaluate HA MW distributions. Synovial fluid parameters were analyzed via linear regression models, revealing that lubricin and HA concentrations were conserved across healthy, high‐motion joints. Lubricin concentrations increased post‐injury in all osteoarthritis models (carpal fragmentation P = .001; talar impact P < .001; femoral trochlear ridge cartilage defect P = .03). Sustained loss of HA was noted post‐arthroscopy following carpal osteochondral fragmentation (P < .0001) and talar impact injury (P < .001). Lubricin may be elevated to compensate for the loss of HA and to protect cartilage post‐injury. Further investigation into the mechanisms regulating lubricin and HA following joint injury and their effects on joint homeostasis is warranted, including whether lubricin has value as a biomarker for post‐traumatic osteoarthritis.

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 – 22 , 39 , similar to that observed in spontaneous canine RCCL in the current study.…”

“…Lubricin also improves wear protection of chemically-grafted HA on mica surfaces 49 . It has been hypothesized that lubricin may be elevated to compensate for the loss of HA by restoring cartilage lubrication after joint injury 39 .…”

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

“…2E-F). 39 The effects of each model on synovial uid lubricin and sulfated glycosaminoglycan concentrations were evaluated using a sandwich ELISA and dimethylmethylene blue (DMMB) assay, respectively (Fig. 3A-D and Supplemental Data 2).…”

“…Increased synovial uid lubricin has been observed in several experimental and naturally occurring equine models of joint disease, including carpal osteochondral fragmentation, tarsal impact injury, full-thickness cartilage defect injury and spontaneous osteochondral fragmentation and osteoarthritis. [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.…”

“…61 Decreased expression of the hyaluronic acid synthases 1 and 3 in the synovitis MCJ compared to the lavage TCJ at 12 hours post-induction suggesting a possible mechanism for the decreased HA concentration seen in this study, though HAS2 is thought to be the primary contributor to synovial uid HA expression. 62 An additional limitation to this study is that differences in baseline concentrations of hyaluronic acid in synovial uid and viscosity exist between the MCJ and the TCJ which complicates the comparison between the synovitis and lavage models 39 ; however, the TCJ is ideal for standing lavage and biopsy, and the use of both carpi and both tarsi enabled a randomized, crossover study design that required fewer horses. The multiplex assay used to test synovial uid for in ammatory cytokines and chemokines is a new assay, and this is the rst publication to describe the use of this assay on equine synovial uid.…”