Abstract

Galectins are potent regulators of cell adhesion, growth and apoptosis in diverse cell types, including chondrocytes and synovial fibroblasts. Elevations in synovial fluid galectin-3 have been observed in rheumatoid arthritis, juvenile idiopathic arthritis and experimental inflammatory arthritis in animal models, whereas galectin-1 is thought to be protective. Less is known about galectins-1 and-3 in osteoarthritis (OA). Therefore, the purpose of this study was: (1) to determine whether galectin-1 and-3 synovial fluid concentrations and synovial membrane and cartilage histochemical staining were altered following osteochondral injury in an experimental equine osteoarthritis (OA) model and (2) to measure galectin-1 and-3 mRNA expression and synovial fluid concentrations in naturally occurring equine carpal OA. Synovial fluid galectin-1 and-3 concentrations were quantified using custom ELISAs in two research horse cohorts undergoing experimental OA induction (n = 5 and 4) and in a cohort of horses with naturally occurring carpal OA (n = 57). Galectin mRNA expression in synovial membrane and cartilage tissue obtained from carpal joints of horses with naturally occurring OA was measured using RT-qPCR, and galectin immunostaining was assessed in synovial membrane and osteochondral tissues in the experimental model (n = 5). Synovial fluid galectin-1 and-3 concentrations increased following experimental carpal osteochondral fragmentation. Cartilage galectin-1 mRNA expression increased with OA severity in naturally occurring disease. The superficial zone of healthy articular cartilage stained intensely for galectin-3 in sham-operated joints, whereas galectin-1 staining was nearly absent. Chondrocyte galectin-1 and-3 immunoreactivity increased following cartilage injury, particularly in galectin-1 positive chondrones. Galectins-1 and-3 are present in healthy equine synovial fluid and increase following post-traumatic OA. Healthy superficial zone chondrocytes express galectin-3, whereas galectin-1 chondrocyte staining is limited predominantly to chondrones and injured cartilage. Further work is needed to clarify the functions of galectins-1 and-3 in healthy and OA joints.

Highlights

  • Galectins are potent regulators of cell adhesion, growth, and apoptosis in diverse tissues and organs, including synovial joints

  • Galectins-1 and-3 are present in healthy equine synovial fluid and synovial tissue but increase in response to osteochondral injury

  • We have demonstrated greater galectin-1 and-3 mRNA expression in healthy equine synovial membrane as compared to healthy articular cartilage [4], suggesting that the synovium may be the predominant source of synovial fluid galectins

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Summary

Introduction

Galectins are potent regulators of cell adhesion, growth, and apoptosis in diverse tissues and organs, including synovial joints. Galectin-1 knockout (KO) mice develop earlier onset and more severe collageninduced arthritis [14], and galectin-3 KO mice have reduced inflammation and bone erosion in response to antigen-induced arthritis as compared to wild-type mice [18]. While both recombinant protein and genetic delivery of galectin-1 are protective in rodent models of collagen-induced arthritis [15,16,17], administration of galectin-3 shRNA protects rodents from collagen-induced arthritis [16]. Classification of galectin-3 as a driver or inhibitor of inflammatory arthritis is likely affected by its intracellular or extracellular localization [6, 19], with rodent knockout models emphasizing intracellular galectin signaling

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