Abstract

Lubricin is an important boundary lubricant and chondroprotective glycoprotein in synovial fluid. Both increased and decreased synovial fluid lubricin concentrations have been reported in experimental post-traumatic osteoarthritis (PTOA) animal models and in naturally occurring joint injuries in humans and animals, with no consensus about how lubricin is altered in different species or injury types. Increased synovial fluid lubricin has been observed following intra-articular fracture in humans and horses and in human late-stage osteoarthritis; however, it is unknown how synovial lubricin is affected by knee-destabilizing injuries in large animals. Spontaneous rupture of cranial cruciate ligament (RCCL), the anterior cruciate ligament equivalent in quadrupeds, is a common injury in dogs often accompanied by OA. Here, clinical records, radiographs, and synovial fluid samples from 30 dogs that sustained RCCL and 9 clinically healthy dogs were analyzed. Synovial fluid lubricin concentrations were nearly 16-fold greater in RCCL joints as compared to control joints, while IL-2, IL-6, IL-8, and TNF-α concentrations did not differ between groups. Synovial fluid lubricin concentrations were correlated with the presence of radiographic OA and were elevated in three animals sustaining RCCL injury prior to the radiographic manifestation of OA, indicating that lubricin may be a potential biomarker for early joint injury.

Highlights

  • Human patients with camptodactyly-arthropathy–coxa vara–pericarditis (CACP) syndrome who lack functional lubricin and Prg[4] knockout mice develop severe, early-onset polyarthropathy, demonstrating the significance of lubricin in chondroprotection and joint h­ omeostasis[11,12,13]

  • Objective, blinded assessment of stifle radiographs revealed that all but three of the RCCL subjects were assigned a radiographic global OA score above the threshold obtained by receiver operating characteristic (ROC) curve analysis (Figs. 1A, 3A)

  • While the exact pathology of canine RCCL remains unknown, it is recognized as either the result of traumatic injury to the ­CCL24 or the result of degenerative CCL disease that eventually leads to ligament rupture secondary to a non-contact injury, similar to that found in female ­athletes[6]

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Summary

Introduction

Human patients with camptodactyly-arthropathy–coxa vara–pericarditis (CACP) syndrome who lack functional lubricin and Prg[4] knockout mice develop severe, early-onset polyarthropathy, demonstrating the significance of lubricin in chondroprotection and joint h­ omeostasis[11,12,13]. Lubricin-deficient synovial fluid from human patients with CAPC syndrome had inferior boundary lubricating ability, and increased joint friction was observed in mice with lubricin loss-of-function m­ utations[13]. In one study investigating human patients with ACL injury, synovial fluid lubricin concentrations were acutely decreased post-injury and gradually returned to values similar to the contralateral knee over the course of a ­year[16]. Similar increases in synovial fluid lubricin have been observed in several studies in both experimentally-induced and naturally occurring PTOA models in ­horses[19,20,21,22]. To the authors’ knowledge, only one prior study has evaluated lubricin in a canine experimental ACL transection model, which revealed increased cartilage lubricin immunostaining depth in injured cartilage; synovial fluid lubricin was not m­ easured[23]. The objectives of this study were to measure synovial fluid lubricin concentrations in healthy canine stifle joints and in joints with spontaneous RCCL and to determine if changes in synovial fluid lubricin correlated with RCCL injury, radiographic evidence of OA, or concentrations of pro-inflammatory cytokines/chemokines in synovial fluid

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