Effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate on synovial fluid chondroitin sulfate 3B3 and 7D4 epitope in a canine cruciate ligament transection model of osteoarthritis

Abstract Objective To evaluate effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate (CS–G–M) on articular cartilage metabolism in dogs with cranial cruciate ligament (CCL) deficient and reconstructed knees, as reflected by concentrations of synovial fluid 3B3, 7D4 and total sulfated glycosaminoglycan (GAG). Methods Sixteen adult dogs that underwent unilateral CCL transection were randomized into four groups. Thereafter, group I ( N =3) had a sham CCL reconstruction, group II ( N =3) had CS–G–M and sham CCL reconstruction, group III ( N =5) had CCL reconstruction, and group IV ( N =5) had CS–G–M and CCL reconstruction. Synovial fluid collected at 0, 1, 3 and 5 months was examined by ELISA for 3B3 and 7D4 epitope, and by DMMB assay for total GAG. Results Synovial fluid from CCL transected knees of CS–G–M treated dogs contained significantly elevated concentrations of 3B3 ( P =0.029), 7D4 ( P =0.036) and 7D4/GAG ( P =0.007) in comparison to controls, in a cross-sectional analysis at 3 months. Furthermore, 7D4 and 7D4/GAG concentrations remained significantly elevated ( P =0.012) in CCL transected knees of CS–G–M treated dogs over the 5 month period. However, when epitope concentrations were expressed as a ratio of CCL-transected to contralateral non-operated knee, treatment effect of CS–G–M was no longer significant. Reconstruction of the CCL had no significant effect on synovial fluid epitope. Conclusions Administration of CS–G–M was associated with altered concentrations of 3B3 and 7D4 epitope in synovial fluid, suggesting that these compounds may act to modulate articular cartilage matrix metabolism in vivo .