Synovium secretome as a disease-modifying treatment for equine osteoarthritis.

This research sought to discover potential new treatments for osteoarthritis in horses by studying substances that cartilage cells (chondrocytes) and joint lining cells (synoviocytes) produce, using a detailed approach known as ‘bottom-up proteomics’. The results suggested that these cells secrete certain proteins that may have the ability to enhance cartilage health and potentially restore normal joint function in horses with osteoarthritis.

Research Methodology

• The investigators used paired equine cartilage explants (tissue extracted from the body for experimental use) and synovial membranes (the tissue that lines the inside of the joint) sourced postmortem from four horses with no reported lameness and apparent joint health at postmortem examination.
• Six groups were created: cartilage alone, synoviocytes alone, and a cartilage-synoviocytes co-culture, each with or without a detrimental protein called Interleukin (IL)-1β.
• To gauge the damaging effect of IL-1β, the researchers measured the level of glycosaminoglycan, a molecule that cushions the joints, which is released into the media from the cartilage. This was verified through a unique assay and a cartilage staining process.
• The liquids from the co-cultures (termed ‘conditioned media’) with and without IL-1β were analysed using the bottom-up proteomics technique.
• Furthermore, gene expression in synoviocytes was examined using reverse transcription-quantitative PCR for the proteins of interest discovered during the proteomic investigation.

Results

• Retention of GAG content was seen in cartilage from co-cultures treated with the detrimental IL-1β protein, suggesting a protective effect of the co-culture environment.
• From 14 identified proteins of interest, four (TIMP3, TNFRSF11B, IGFBP2, and A2M) underwent gene expression analysis in synoviocytes.
• The gene expressions of TIMP3 and TNFRSF11B were significantly higher in synoviocytes from co-cultures treated with IL-1β compared to the controls. However, contrary to expectations, IGFBP2 gene expression was significantly lower in the tested synoviocytes compared to the controls.
• Gene expression of A2M in synoviocytes was found similar across experimental groupings.

Conclusion

• From these results, the researchers propose that synoviocytes might have a secretome (a group of substances that cells release) with bioactive factors that could potentially offer a beneficial solution in the treatment of osteoarthritis by restoring joint balance.