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Abstract
Fat mass dysregulation is a marked characteristic of overweight and obesity. Obesity is, historically, a classic risk factor for osteoarthritis development and progression and shares with osteoarthritis a huge societal impact but also several common biochemical features that are strongly related to the low-grade inflammatory status. Even though OA has been considered during decades a disabling degenerative disease related to mechanical, age and genetic factors with poor inflammatory component, the current consensus is that OA, in particular OA associated with metabolic alterations, is a global muscle-skeletal diseases in which pro-inflammatory and catabolic mediators, most of them produced by a dysregulated visceral or periarticular white adipose tissue (WAT), are at play. The coexistence of obesity and OA is a clinical reality and is changing the traditional view of this degenerative disorder. Thus, chronic low-grade inflammation is a common characteristic shared by both obesity and OA. It has been demonstrated that obesity increases the incidence of OA, particularly in weight-bearing joints such as knees. However, the fact that obese individuals have an increased risk of developing OA in non-weight bearing joints such as hands and wrists suggests that factors produced by WAT play a role in the onset and/or progression of OA. In addition to a growing body of evidence demonstrating that obesity has a direct mechanical effect joint cartilage, recent research shows that pro-inflammatory factors produced by WAT (collectively known as adipokines) promote further inflammation and degradation of cartilage, also influencing the whole joint environment (i.e. synovium, muscle, bone and immune cells). Accumulating evidence shows another potential source of inflammatory adipokines in the joint is the Hoffa infrapatellar fat pad. Adipokines including leptin adiponectin, visfatin and lipocalin 2 have been demonstrated to exhibit a wide spectrum of biological activity including the activation of pro-inflammatory and catabolic pathways mediated by elevated levels of NO, ROS, MMPs and PGE2. The discovery of adipokines has made a major contribution to our understanding of the complex relationship between diabesity and OA, encompassing a variety of factors that include the immune system, metabolism and biomechanics. A critical aspect that must constantly be borne in mind is that diabesity and OA share a low-grade inflammatory state that heavily influences the course of OA progression. Therefore, the prevention and correction of diabesity should be the first line approach for tackling the detrimental effects of weight gain, adiposity and altered metabolic WAT function in OA. The aim of this lecture is to summarize the role of adipokines in bone and cartilage function, as well as in inflammatory and degenerative joint disease. We discuss clinical implications and then survey attempts to exploit this role for therapeutic gain, which holds potential as a novel approach for drug development in bone and joint disease.
Disclosure of Interest None declared