Low adiponectin content in blood plasma indicates positive effects of a specific collagen hydrolysate for age-related osteoarthritis in mice

Purpose: The aim of this study was to investigate the influence of a specific collagen hydrolysate on the progression of osteoarthritis in a validated mouse model. Moreover, the involvement of adiponectin in the process of osteoarthritis was investigated. Methods: All animal protocols were approved in accordance to the Institutional Animal Care and Use Committee at the University of Kiel, Germany. The efficacy of a specific collagen hydrolysate (FORTIGEL GELITA AG, Germany) was tested in a randomly assigned placebo-controlled animal study against bovine serum albumin as placebo over a time period of six months. Male STR/ort mouse which develops spontaneously osteoarthritic lesions of the knee joint by 35 weeks of age were used for the experiments. Mice were maintained individually under standardized conditions with open access to food and water and a daily orally dosage of 0.15 mg/g body weight of FORTIGEL or placebo. The development of osteoarthritis in knee joints was scored 0 - 4 in haematoxylin stainings. Osteoarthritis was assessed as 0 = no apparent changes; 1 = loss of superficial zone; 2 = defects limited above tidemark; 3 = defects extending to calcified cartilage and 4 = exposure of subchondral bone. Additionally to histochemical classification the plasma adiponectin levels in the STR/ort mice were tested over the time of experimentation. A possible correlation between grade of osteoarthritis and different osteoarthritic risk factors like obesity, aging and moreover, of adiponectin plasma level were assessed. Analysis of variance was performed using the Kruskal-Wallis test. For comparison of collagen hydrolysate and placebo treated animal cohorts the Mann-Whitney U-test was used. Correlations of osteoarthritic changes, weight gain and adiponectin plasma level were analyzed according to Pearson. P values < 0.05 were considered to be significant. Results: In 12 weeks old non-treated STR/ort mice no osteoarthritic changes of the cartilage or slightly defects of the superficial zone were observed (Fig. 1 a, b). With age grade of osteoarthritis increased significantly and cartilage destructions above the joint tidemark with partially exposed subchondral bone was seen. In addition to degenerative cartilage changes with age male STR/ort mice become significantly obese. Mean body weight of STR/ort mice increased over the experimental period of six month from 36 to 49 g (Fig. 2). Over this time an increased age-related adiponectin plasma level was determined (Fig. 3). Out of our findings we computed a significant correlation of an increased plasma adiponectin level and potentiated grade of osteoarthritis in untreated animals. Moreover, body weight gain and an increased grade of osteoarthritis were also significantly correlated (Fig. 4 a). No correlation was seen between adiponectin amount and body weight in the mouse model (Fig. 4 b). The determined grade of osteoarthritis decreased significantly by FORTIGEL administration in comparison to the placebo treated animals (Fig. 5). Moreover, FORTIGEL treatment seems to improve osteoarthritis related immobility of the animals reflected by a less body weight gain (Fig. 6). The fact that FORTIGEL diminishes osteoarthritis will be confirmed by a lower adiponectin level in the plasma of these animals (Fig. 7). Conclusions: Osteoarthritic changes are well correlated with body weight and adiponectin plasma level. In contrast, no correlation was found between adiponectin amount and body weight gain. A low adiponectin level and reduced body weight, after FORTIGEL treatment suggested that FORTIGEL could be a potential disease modifying agent for the treatment of degenerative joint diseases. Our animal study demonstrates that incidence of severe joint destruction was clearly reduced after FORTIGEL treatment and that adiponectin is a suitable indication biomarker for osteoarthritis.