Effect of intramuscularly administered polysulfated glycosaminoglycan on articular cartilage from equine joints injected with methylprednisolone acetate

Abstract

Summary Intra-articularly administered, long-acting corticosteroids are a beneficial treatment for many equine joint disorders because they alleviate inflammation and signs of pain, but they also exert detrimental effects on the biochemical composition and morphologic features of articular cartilage. Chondroprotective drugs have been shown to mitigate some of the deleterious effects of intra-articularly administered corticosteroids on articular cartilage of laboratory animals. Twenty-one ponies were assigned at random to receive 1 of 3 treatments in the right middle carpal joint. Group-1 ponies (n = 8) had methylprednisolone acetate (mpa; 0.2 mg/kg of body weight) and saline solution administered intra-articularly and im, respectively. Group-2 ponies (n = 9) received mpa (0.2 mg/kg) and polysulfated glycosaminoglycan (gag; 2 mg/kg). Group-3 ponies (control; n = 4) had saline solution administered intra-articularly and im. The corticosteroid or saline solution was injected into the right middle carpal joint on day 1. The im administered polysulfated gag or saline solution was administered at the same time, then was repeated every 3 days for 20 days. Ponies were euthanatized 21 days after initial injection by overdose of pentobarbital sodium. The cartilage of younger ponies was significantly (P < 0.05) more responsive to the proteoglycan-depleting effects of mpa. Ponies < 10 years old of groups 1 and 2 had significantly (P < 0.05) lower gag content in the articular cartilage than did control ponies. Systemic treatment with polysulfated gag did not result in a protective effect against proteoglycan loss from the articular cartilage. Twenty-one days after mpa injection, difference in [35S]sulfate incorporation into proteoglycan, between either mpa-treated group and the control group, was not significant. There was an approximate tenfold increase in keratan sulfate concentration in synovial fluid from mpa-treated joints, compared with control joints. Chondroprotective effect of polysulfated gag on the basis of keratan sulfate release from the articular cartilage into the synovial fluid was not observed. Methylprednisolone acetate caused a decrease in the fibronectin content of articular cartilage, but there was no effect of polysulfated gag on the fibronectin content of mpa-treated articular cartilage.