Is Synovial Macrophage Activation the Inflammatory Link Between Obesity and Osteoarthritis?

Abstract

Osteoarthritis (OA) is the most common musculoskeletal disease, affecting nearly 25 % of the world population (WHO reports), leading to pain and disability. There are as yet no clinically proven therapies to halt OA onset or progression; the development of such therapies is, therefore, a national as well as international research priority. Obesity-related metabolic syndrome has been identified as the most significant, but also an entirely preventable risk factor for OA; however, the mechanisms underlying this link remain unclear. We have examined the available literature linking OA and metabolic syndrome. The two conditions have a shared pathogenesis in which chronic low-grade inflammation of affected tissues is recognized as a major factor that is associated with systemic inflammation. In addition, the occurrence of metabolic syndrome appears to alter systemic and local pro-inflammatory cytokines that are also related to the development of OA-like pathologies. Recent findings highlight the importance not only of the elevated number of macrophage in inflamed synovium but also the activation and amplification of the inflammatory state and other pathological changes. The role of local inflammation on the synovium is now considered to be a pharmacological target against which to aim disease-modifying drugs. In this review, we evaluate evidence linking OA, synovitis and metabolic syndrome and discuss the merits of targeting macrophage activation as a valid treatment option for OA.

Modulatory effects of different exercise modalities on the functional connectivity of the periaqueductal grey and ventral tegmental area in patients with knee osteoarthritis: a randomised multimodal magnetic resonance imaging study

“…PD-1 is a cell surface protein that has a role in regulating the immune response by down-regulating the immune system, and is a key serum biomarker in the process and treatment of KOA. 63,64 The neurotransmitter, DA, is an important molecule in communication between the nervous and immune systems, and the VTA is an important dopaminergic brain region. 65 Our finding that decreased VTAeMOPFC rsFC has a significant association with PD-1 serum concentrations suggests that its anti-immune function might play a modulatory role in pain relief after exercise via VTAeMOPFC rsFC modulation.…”

Lipidomic identification of plasma lipids associated with pain behaviour and pathology in a mouse model of osteoarthritis

“…The role of a broad spectrum of lipid mediators, including fatty acids, sphingolipids, and eicosanoids in cartilage degradation in OA is increasingly recognised (Masuko et al 2009). Lipid dysregulation in all compartments of the joint is considered an important feature of this disease (Courties et al 2015;Sun et al 2016). Lipidomics, which can be defined as the system-wide characterization of lipids and their interaction with other biochemicals and cells (Spener 2003), has dramatically advanced over the past decade, due to developments in analytical technologies, such as mass spectrometry (MS) and chromatography, reviewed in (Hyotylainen and Oresic 2016).…”

Associação entre osteoartrite de joelho e síndrome metabólica em pacientes idosos não institucionalizados

“…[10][11][12][13] Some researchers point out that these mechanisms seem to have direct systemic effects on the joint and could damage cartilage, bone, and synovial tissue, regardless of the excess weight. [14][15][16] Such damages, arising from OA, affect millions of people and present as main characteristics pain, joint stiffness, and decline in functionality, such as impairment in performance of daily living activities (DLA). 17 The research also highlights that its incidence increases with the advancement of age, particularly in individuals above 60 years old.…”

“…17 The research also highlights that its incidence increases with the advancement of age, particularly in individuals above 60 years old. 9,[14][15][16][17] Considering the changes in body composition during the aging process and the importance of OA as a factor of functional impairment and of MS as a risk factor for cardiovascular disease, the present study aimed to analyze the association between knee OA and MS in non-institutionalized elderly patients. And, considering the scarcity of studies of this nature, especially with this population, this research is necessary even to direct future public health policies for the elderly.…”