Background Osteoarthritis (OA) is primarily characterized by cartilage and bone erosion as well as the formation of osteophytes. These processes are mediated by an increased osteoblast activity, which is -in turn- regulated by the Wnt signaling pathway. Obesity is a recognized risk factor in OA, yet little is known about the interaction between adipose tissue-derived factors including adipokines and bone formation. Histological analysis of OA osteophytes showed the presence of adiponectin, resistin and visfatin in osteophytes. In addition, OA osteoblasts respond to adipokines in a specific manner, e.g. adiponectin induces inflammatory mediators in these cells. These effects can be further modulated by activation of the Wnt-signaling pathway. Hence, in this context, the effects of adiponectin, resistin and visfatin on Wnt signaling in OA osteoblasts were analyzed.
Methods Osteoblasts were isolated from OA bone tissue obtained during joint replacement surgery. Cultured osteoblasts were stimulated with adiponectin, resistin and visfatin. Additionally, a co-stimulation with Wnt3a or DKK1 was performed. The Wnt signaling pathway of stimulated vs. non-stimulated osteoblasts was analyzed for adipokine-mediated effects using immunoassays for IL-6, DKK1 and sclerostin, and by real-time PCR for axin2.
Results Stimulation of OA osteoblasts with adiponectin, resistin or visfatin did not alter the release of the Wnt inhibitor DKK1 compared to the unstimulated controls. The level of the secreted Wnt inhibitor sclerostin was below the detection level of the immunoassay for both, adipokine-stimulated osteoblasts as well as for unstimulated control cells. Also, the expression of axin2, a direct target gene of the Wnt signaling showed no significant differences in OA osteoblasts after adipokine-stimulation compared to the unstimulated control. A co-stimulation with adiponectin, resistin or visfatin in combination with Wnt3a or DKK1 had no synergistic influence on the Wnt-mediated IL-6 release of OA osteoblasts.
Conclusions The adipokines adiponectin, resistin and visfatin are present in osteoblasts in OA osteophytes, and adipokines such as adiponectin increase the release of inflammatory mediators by OA osteoblasts. However, the observed adipokine-mediated effects do not include induction of Wnt-signaling. Therefore, the involvement of adipokines in OA osteophyte formation via osteoblasts appear to be independent of Wnt signaling.
Acknowledgements Funded by the ANCYLOSS project of the German Ministry of Research and Education (BMBF).
Disclosure of Interest None declared