Adiponectin in Osteoarthritis: Pathophysiology, Relationship with Obesity and Presumptive Diagnostic Biomarker Potential

Abstract

Osteoarthritis (OA) is a multifactorial, irreversible age- and obesity-induced joint degenerative disease, with an increasing incidence in developed countries. With a pathophysiology and etiology that are currently under-investigated, the only available disease-modifying treatment relies solely on total joint arthroplasty, which entails major economic burdens. Recently, the research focus has shifted towards the evaluation of metabolically active mediators secreted by the adipose tissue, which could be potential targets for a better understanding of the mechanisms involved in OA onset and development. Of note, adiponectin has drawn a great deal of attention, since it is the most abundant type of circulating adipokine and has been highly associated with OA occurrence. Thus far, studies have been controversial in establishing whether adiponectin possesses a destructive or protective role in OA development. Therefore, we critically and systematically reviewed, herein, the roles of adiponectin in the pathophysiology of OA, the link between obesity, adiponectin expression and the progression of OA, as well as its potential role as a future biomarker for a more optimized and reliable diagnosis of this degenerative disorder.

Obesity, Inflammation, and Immune System in Osteoarthritis

“…Furthermore, the cellular interaction between macrophages and adipocytes resulted in adipose-associated inflammatory responses. The characteristic M1 phenotype for obesity has been known to increase the production of adipokines, and in turn adiponectin which regulates the obesity-induced inflammation in OA and modulates immune responses ( 12 , 172 , 173 ). The concentration of adiponectin was reported to be higher in concentration in OA patients in comparison with controls.…”

“…Adipokines are a key player that regulates the homeostasis in inflammation, immunity, reproduction, angiogenesis, fibrinolysis, regulating appetite, coagulation, and insulin sensitivity ( 10 ). It is becoming evident with piles of novel studies that correlate obesity-induced adipokine production which leads to the onset of OA ( 11 , 12 ). A large genome-wide associated study was run to identify the susceptibility risk loci.…”

Adipokine Signaling Pathways in Osteoarthritis

“…It’s close association with OA have been widely reported in literature ( Collins et al, 2020 ). Clinical data has shown that there was a positive correlation between synovial adipokine level and OA activity index in elderly women with knee OA ( Eldjoudi et al, 2022 ; Ilia et al, 2022 ).…”

Effects of Obesity on Medial Tibiofemoral Cartilage Mechanics in Females—An Exploration Using Musculoskeletal Simulation and Probabilistic Cartilage Failure Modelling

“…Taking into account the modelled walking volume and measured velocity, the current investigation produced similar axial joint forces and cartilage strains to previous musculoskeletal modelling, simulation and in vivo analyses [ 12 , 34 , 35 ] as well as medial tibiofemoral failure probabilities to epidemiological incidence rates in both healthy weight and obese groups [ 11 , 13 , 35 , 66 ]. However, OA is recognized as a multifactorial joint disease [ 14 ] in which chronic low-grade inflammation plays an important role [ 17 , 18 , 20 , 21 ], therefore as the computational model of medial tibiofemoral cartilage failure probability adopted in the current investigation did not account for adipokine levels, may serve as a limitation to this investigation. Future developmental analyses are necessary to develop a more complex and computationally heavy probabilistic model, capable of quantifying the interaction between mechanical and biochemical mechanisms of medial tibiofemoral OA.…”

“…There has been considerable research interest concerning the potential role of adipokines in the pathogenesis of OA [ 19 ]. Previous analyses have confirmed that levels of leptin and resistin were greater in obese individuals with knee OA in relation to healthy controls and that levels of these adipokines were also associated with radiographic OA stage [ 20 ], indicating that they may play a significant role in the multifactorial nature of knee OA pathophysiology [ 21 ].…”