Amelioration of lapine osteoarthritis by treatment with glycosaminoglycan–peptide association complex (Rumalon)

Abstract

The chondroprotective potential of glycosaminoglycan–peptide association complex (GP‐C) was examined in the medial meniscectomy model of lapine osteoarthritis (OA). Prophylactic treatment with increasing doses of intramuscular GP‐C (0.05–0.5 ml/kg) caused a significant reduction in OA lesion area and histologic scores, and the effect on disease activity appeared to be dose related. The DNA and uronic acid contents of OA tissue were unaffected by prophylactic treatment with GP‐C. However, levels of hydroxyproline in OA cartilage increased to near control levels with prophylactic treatment. Cartilage levels of active and total metalloproteinases that digest proteoglycans were elevated in rabbits with OA; prophylactic treatment with low‐dose GP‐C (0.05 ml/kg) produced a significant reduction in active, but not total, enzyme. Cartilage levels of tissue inhibitor of metalloproteinases in animals with OA were comparable with control levels, but rose with increasing doses of GP‐C. We also investigated GP‐C as a therapeutic treatment in animals that had already developed OA lesions. Carbon black retention and histologic score returned to near‐normal after therapeutic treatment with GP‐C. Uronic acid and hydroxyproline levels were decreased in OA cartilage. Therapeutic treatment with GP‐C had no statistically significant effect on uronic acid levels, but was associated with increased hydroxyproline content in the cartilage. The changes in metalloproteinase and metalloproteinase inhibitor were similar to those found in the studies of prophylactic treatment. The findings in this animal model may help explain some of the beneficial effects of GP‐C in human OA.

Chondroitin sulphate extracted from antler cartilage using high hydrostatic pressure and enzymatic hydrolysis

“…In addition, CS shows a dose-dependent increase in free radical scavenging [2]. This antioxidant activity, caused by the chelation of transition metals such as Cu 2+ and Fe 2+ , is also believed to be partially responsible for the chondroprotective effects of CS, as oxidative stress has been shown to increase the risk and effects of osteoarthritis [1], [7], [3], [5], [33]. CS is an important constituent for the preservation of corneal tissues.…”

Characterization of Glycosaminoglycans by15N NMR Spectroscopy and in Vivo Isotopic Labeling

“…As a part of the ECM they influence numerous physiological processes, including organogenesis/growth control,5, 6 cell adhesion,7 angiogenesis,8 wound healing,9, 10 tumorigenesis,10, 11 morphogenesis,12, 13 inflammation,14–16 haemostasis,17, 18 and neural development/regeneration 19–22. GAGs also participate as receptors of various pathogens during the process of infection,23 and they have found applications in the treatment of diseases,24–26 for example, in the use of heparins for the treatment of acute coronary conditions 27–30. In many cases it is clear that biological function is dependent on specific structures (motifs) along the backbone of these complex polymeric carbohydrates 3, 31.…”

The Free Radical-Scavenging Property of Chondroitin Sulfate From Pig Laryngeal Cartilage in Vitro

“…1992). ChS from bovine trachea has been shown to have chondroprotective effects in experimental animals mainly due to its free radical scavenging activity (Dean et al. 1991; Campo et al.…”

“…Also, the molecular mass, carboxyl groups and positions of sulfate ester involved in its bioactivity depend on the origin of the tissue, its age and the species (Beaty and Mello 1987;Kuettner et al 1992). ChS from bovine trachea has been shown to have chondroprotective effects in experimental animals mainly due to its free radical scavenging activity (Dean et al 1991;Campo et al 2002). Chondroitin-4-sulfate, a basic component of the extracellular matrix of the artery wall, inhibited Cu 2+induced low-density liproprotein (LDL) and may contribute to protecting LDL against oxidation in arterial intima (Albertini et al 1997).…”