Systemic lipid peroxidation and skeletal tissues metabolism in animals with simulated posttraumatic osteoarthrosis

Abstract

The role of individual factors in the progressing of degenerative and dystrophic changes of articular cartilage as the focus of pathologic changes in posttraumatic osteoarthrosis (PTOA) has been studied comprehensively. However, no single concept of pathogenetic mechanisms leading to the formation of permanent changes in the affected joint has been represented yet. Therefore, the investigation of lipid peroxidation and skeletal tissues metabolism in animals with simulated PTOA is a challenging and important issue. In 28 non-linear male rats (12 intact control animals and 16 experimental animals with simulated knee OA) we studied the lipid peroxidation rate by the level of lipid hydroperoxides, antioxidant system activity by the indicants of total antioxidant, and thiol statuses. The destruction processes in skeletal tissues were evaluated by the level of hyaluronan, a cartilaginous tissue marker, and subchondral bone turnover makers (fibroblast growth factor-23, osteoprotegerin, sclerostin, osteocalcin). In rats with simulated PTOA, we observed the activation of lipid peroxidation with the accumulation of lipid hydroperoxides in systemic blood flow along with the insignificant decrease of thiol status indicant while the normal antioxidant activity is maintained. We also revealed the significant increase of biopolymer hyaluronan (p<0.05) in a negative change of turnover regulation marker (the significant increase in fibroblast growth factor-23 (p<0.05) with the emerging trend for osteoprotegerin and sclerostin decrease) and bone formation marker (high osteocalcin) as compared to the intact controls. Our findings confirmed that animals with simulated PTOA featured rearranging of skeletal tissues as compared to intact animals. This process involved degenerative destruction of both chondral and osseous tissues along with profound prooxidant activity and relative incompetence of the thiol system while the indicants of general antioxidant activity remain normal. This suggests the importance of the analyzed markers in PTOA pathogenesis and determined the prospects of their use for the evaluation of therapy efficacy.