Metabolic stress-induced joint inflammation and osteoarthritis

Abstract

Osteoarthritis (OA) is a heterogeneous disorder with several risk factors. Among them, obesity has a major impact on both loading and non-loading joints. Mechanical overload and activity of systemic inflammatory mediators derived from adipose tissue (adipokines, free fatty acids (FFA), reactive oxygen species (ROS)) provide clues to the increased incidence and prevalence of OA in obesity. Recently, research found greater OA prevalence and incidence in obese patients with cardiometabolic disturbances than "healthy" obese patients, which led to the description of a new OA phenotype - metabolic syndrome (MetS)-associated OA. Indeed, individual metabolic factors (diabetes, dyslipidemia, and hypertension) may increase the risk of obesity-induced OA. This review discusses hypotheses based on pathways specific to a metabolic factor in MetS-associated OA, such as the role of advanced glycation end products (AGEs) and glucose toxicity. A better understanding of these phenotypes based on risk factors will be critical for designing trials of this specific subset of OA.

Economic impact of lower-limb osteoarthritis worldwide: a systematic review of cost-of-illness studies

“…Actually, from a public health perspective, a diagnosis based on both clinical and radiological features is recommended (53). In addition, some authors recently suggested separating OA by phenotypes, reflecting different risk factors, comorbidities and potentially pathogenic pathways (7,61). Comorbidities such as obesity are closely related with lower-limb OA (62).…”

An update on the pathophysiology of osteoarthritis

“…Cohort studies have demonstrated that after age, obesity and metabolic disease are major risk factors for the development of OA (4,5). OA is now generally accepted to be an inflammatory and biomechanical whole-organ disease that is influenced by a number of factors including joint shape and dysplasia (6), obesity (7), synovitis (8-10), complement proteins (11), systemic inflammatory mediators (1,12), inflammaging (13,14), innate immunity (15), the low-grade inflammation (16) induced by metabolic syndrome (1,17) and diabetes mellitus (18). However, despite the fact that all joint tissues are potentially implicated in disease initiation and progression in OA, it is the articular cartilage component that has received the most attention in the context of aging, injury and disease (2).…”

Myrtol improves post‑traumatic knee osteoarthritis by regulation of reactive oxygen species, transforming growth factor β1 and apoptosis in a mouse model

“…Over-proliferation of synovial cells is originated from comparative deficiency of synovial cell apoptosis (21). In recent years, research has detected that the second messenger ROS is associated with PTKO damage (22). The oxidative stress caused by ROS is able to damage mitochondrial respiratory chain.…”

“…Previous studies have suggested that ROS can regulate cell proliferation, differentiation, programmed cell death and aging. A small increase in ROS level promotes cell proliferation (22,24), while a moderate increase can induce cell apoptosis, and high ROS levels directly cause necrocytosis. High concentration of ROS can directly or indirectly damage the mitochondrial membrane structure, induce voltage reduction of mitochondrial membrane, and lead to mitochondrial bulging (21).…”