Background/Purpose: Hydrogen sulphide (H₂S) is recognized as a therapeutic target in osteoarthritis (OA). Exogenous supplementation with synthetic salts in in vitro models of OA has been shown to exert anti-inflammatory effects and results in reduced cartilage degradation. Here we evaluated the effects of an intra-articular treatment with an H₂S-producing compound in an in vivo model of OA.

Methods: Experimental OA was induced in the left knees by transecting the medial collateral ligament and removing the medial meniscus. Animals were randomized into 3 groups (6 rats/group). Group 1 (intra-articular sulphide, IS): A single intra-articular injection of GYY4137 (200 uM in saline, 50 ul) at day 7. Group 2 (intra-articular control, IC): A single intra-articularly injection of vehicle (saline, 50 ul) at day 7. Group 3 (Surgical control, C): No treatment. Gross evaluation of the animals was performed at days 0 (before surgery), 7, 15 and 40 (euthanasia). Histopathological changes in articular cartilage and synovium were evaluated with the Mankin Score (MS) and the Krenn Score (KS), respectively.

Results: At day 7 after surgery animals in all groups had increased left knee perimeter, deep pain levels and showed worse performance in a Rotarod test (number of falls [n#f] and time to 1^st fall [t1f], Table 1). At day 40, there was no significant improvement in either of these parameters in groups C or IC (except IC n#f that returned to pre-surgical levels). In IS values were significantly improved with respect to day 0 and both C and IC groups at days 15 and 40 (Table 1). Also left knee perimeter and deep pain levels had subsided.

Histology showed no significant differences among groups in the lateral tibial plateau (TP) or femoral condyle (FC) separately or in the compartment as a whole. Conversely, MS in the medial compartment were significantly better in the IS group vs the C group, both when considering TP or FC separately, and for the whole compartment (Table 2). No significant differences were found among groups on the Krenn Scores.

Conclusion: Intra-articular H₂S administration (200 uM GYY4137 in 50 ul saline) can reduce the severity of cartilage destruction in an in vivo model of OA as compared to no treatment or a vehicle control. H₂S also led to a reduction in inflammation and pain levels as demonstrated by gross examination and a performance test. Therefore, hydrogen sulphide is a viable pharmacological candidate for OA treatment and should be further tested, including human clinical trials.