Pathogenic Mechanisms and Therapeutic Approaches in Obesity-Related Knee Osteoarthritis

The knee is the joint most frequently involved in osteoarthritis, a common joint disorder in the adult population that is associated with significant chronic joint pain, reduced mobility and quality of life. Recent studies have established an association between obesity and the development of knee osteoarthritis that goes beyond the increased mechanical load on the knees as weight-bearing joints. This link is based on the maintenance of a chronic low-grade inflammation, altered secretion of adipokines by the adipose tissue and development of sarcopenia. Major adipokines involved in the pathogenesis of obesity-related knee osteoarthritis include adiponectin, which appears to have a protective effect, as well as leptin, resistin and visfatin, which are associated with higher pain scores and more severe structural damage. Joint pain in knee osteoarthritis may be both nociceptive and neuropathic and is the result of complex mechanisms driven by nerve growth factor, calcitonin gene-related peptide and pro-inflammatory cytokines. The role of endogenous cannabinoids and gut microbiota in common mechanisms between obesity and knee pain has recently been studied. The aim of the present review is to highlight major pathogenic mechanisms in obesity-related knee osteoarthritis with special attention on pain and to comment on possible therapeutic approaches.