Abstract:

BACKGROUND: H2S is an important inflammatory regulator, which widely exists in various tissues and organs of human body and plays an important role in many systemic diseases.
OBJECTIVE: To investigate the effect of H2S on articular cartilage degeneration in rabbit knee osteoarthritis model and to explore the therapeutic effect of H2S on osteoarthritis.
METHODS: Thirty-two New Zealand white rabbits were randomly divided into four groups: blank control, osteoarthritis, H2S, and H2S inhibition groups (n=8/group). Blank control group was not treated, the other three groups were used to establish the osteoarthritis model by modified Hulth method, and were then injected with normal saline, NaHS diluent (60 μmol/L) and H2S synthase inhibitor (aminooxyacetic acid, 37.5 mg/kg; propargylglycine, 60 mg/kg) 1 mL each into the knee joint cavity once a week for 6 weeks. The study was approved by the Laboratory Animal Ethical Committee of Qingdao University, approval No. AHQU-MAL2018032.
RESULTS AND CONCLUSION: (1) Pathological changes: the morphology of articular cartilage in the blank control group was normal; the degeneration of articular cartilage in the osteoarthritis group was serious; the degeneration of articular cartilage in the H2S group was mild; and the degeneration of articular cartilage in the H2S inhibition group was more serious than that in the osteoarthritis group. (2) Mankin’s score showed that the scores in the osteoarthritis, H2S and H2S inhibition groups were significantly higher than those in the blank control group (P < 0.05); the scores in the H2S group were lower than those in the osteoarthritis group, and the scores in the H2S inhibition group were significantly higher than those in the osteoarthritis group (P < 0.05). (3) Type II collagen staining showed that compared with the blank control group, the positive staining of type II collagen in the osteoarthritis group was significantly lower and unevenly distributed; the positive staining of type II collagen in H2S group was higher than that in osteoarthritis group; the positive staining of type II collagen in H2S inhibition group was significantly lower and the superficial layer was defective. (4) Compared with the osteoarthritis group, the mRNA expression levels of matrix metalloproteinase-1, matrix metalloproteinase-3 and matrix metalloproteinase-13 in articular cartilage were decreased in the H2S group, and increased in the H2S inhibition group compared with the osteoarthritis group. (5) These results show that H2S can inhibit the mRNA expression of matrix metalloproteinase-1, matrix metalloproteinase-3 and matrix metalloproteinase-13 in articular cartilage, reduce the degradation of type II collagen in articular cartilage, and protect articular cartilage in osteoarthritis.

Key words: osteoarthritis, hydrogen sulfide, type II collagen, matrix metalloproteinase, rabbits, articular cartilage, soft tissue construction, tissue engineering