Intra-articular 2.5% polyacrylamide hydrogel alters synovial immune pathways in equine experimental osteoarthritis.

Intra-articular 2.5% iPAAG modulates synovial immune and inflammatory pathways, suggesting a mechanistic basis for OA treatment.

This study investigated the transcriptomic effects of intra-articular 2.5% polyacrylamide hydrogel (2.5% iPAAG) on synovial tissues in an equine experimental osteoarthritis (OA) model. Osteoarthritis was surgically induced in one middle carpal joint of 16 horses (2–5 years old) via osteochondral fragment creation combined with high-speed treadmill exercise, while the contralateral limb served as a sham control. At day 14 post-surgery, joints were injected with either 2 mL of 2.5% iPAAG or saline (n=8 per group). Synovial biopsies were collected at days 0 and 70, and synovial fluid (SF) at multiple timepoints through day 70. RNA extracted from synovial tissue and SF cells underwent transcriptomic sequencing to identify differentially expressed genes and enriched pathways. In iPAAG-treated synovium at day 70, upregulation of innate immune activation pathways was observed alongside reduced metabolic, cell cycle, and growth factor signaling. The most pronounced transcriptomic effects in SF cells occurred at day 28 (14 days post-treatment), characterized by downregulation of TNF-α inflammatory pathways and T-cell/lymphocyte signaling. These findings suggest that 2.5% iPAAG modulates immune and inflammatory signaling following synovial tissue integration, potentially contributing to its therapeutic effects in OA. Study limitations include use of an acute, experimentally induced OA model, which may not fully replicate naturally occurring chronic OA. Overall, transcriptomic analysis supports immune and signaling pathway modulation as a key mechanism of action for 2.5% iPAAG in equine joint disease.

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