Adiponectin serum levels and disease severity in the STR/Ort mouse model of osteoarthritis

Abstract

Purpose: Adiponectin, an adipokine secreted from adipose tissue into the bloodstream, is involved in the modulation of different metabolic processes including glucose uptake and fatty acid oxidation. This adipokine acts via two receptors, AdipoR1 and AdipoR2, expressed mainly in the skeletal muscle and liver, respectively, but also in chondrocytes. Adiponectin signal transduction by AdipoR1 and AdipoR2 involves the activation of many signaling molecules like Peroxisome proliferatoractivated receptor gamma (PPARg) and 5' AMP-activated protein kinase (AMPK). Unlike other adipokines, whose production is increased with obesity, adiponectin serum levels decrease with increasing weight. The STR/Ort mouse is a model of spontaneous osteoarthritis (OA) that shows a human-like hyperlipidemic condition and is characterized by a very early pathology development. Furthermore, these animals have serum levels of adiponectin much lower than other mouse strains. It was suggested that systemic (plasma) and local (synovial fluid) adipokine levels would be associated with cartilage degeneration and synovial inflammation, linking obesity and adiposity with inflammation and pathology in OA patients. Moreover, a down-regulation of adiponectin receptors was recently reported in human OA chondrocytes. These observations indicate a possible protective role for adiponectin in the development of osteoarthritis. The purpose of our study was to establish a possible relationship between OA development and hypoadiponectinemia in this model. Methods: STR/Ort and CBA mice were recruited at 6 months (26 weeks) of age and euthanized. Serum was obtained from blood samples taken from vena cava at sacrifice, using Microvette® CB 300 capillary tubes (Sarstedt). Knee joints were collected, processed for histology and blindly scored according to both Mankin's and OARSI methods. Adiponectin levels were evaluated from serum samples by a commercially available kit (Bertin Pharma, cat. A05187). Correlation between the OARSI score and adiponectin levels was examined using Spearman's rank correlation test. Results: Adiponectin serum levels in STR/Ort mice at 26 weeks of age were significantly lower compared to CBA mice at the same age (12.5mg/ ml ± 0.65 and 23.9mg/ml ± 0.98 respectively). We observed a significant negative correlation (p ¼ 0.007) between adiponectin levels and weight in STR/Ort mice but not in CBA mice. Among the 6 CBA mice tested, 10 of the 12 knees examined showed no signs of OA (mean OARSI score ¼ 0.3 and Mankin's score ¼ 0.3). Conversely, in the 17 STR/Ort mice only 1 of 34 knees examined showed no signs of OA, while all the other knees showed high level of cartilage damage (mean OARSI score ¼ 14.1 and Mankin's score ¼ 7.9), as revealed in all histopathological parameters evaluated. There was a negative correlation between adiponectin levels and disease severity (as measured by OARSI score), reaching statistical significance (p ¼ 0.04) when considering the less damaged knee. Conclusions: This study, while confirming that adiponectin serum ...

Adiponectin signalling in bone homeostasis, with age and in disease

“… 86 In contrast, serum adiponectin concentrations negatively correlated with cartilage lesions and OA severity in adolescent (26 weeks old) STR/Ort mice, suggesting adiponectin has a protective role in a human-like murine OA model. 87 It is difficult to make any definitive conclusions based on the currently available data on whether changes in adiponectin levels represent part of the molecular mechanism driving pathology of OA, or are part of the protective response to the on-going joint damage. As such these concepts need to be explored further taking into account the aforementioned confounding factors.…”