Synovial Macrophages: Potential Key Modulators of Cartilage Damage, Osteophyte Formation and Pain in Knee Osteoarthritis

Abstract

Synovitis is common in knee OA patients and a known contributor to disease incidence and progression. Macrophages are the most common immune cell type present in this inflamed synovial tissue and expectedly contribute both directly and indirectly to OA progression through the induction of inflammatory mediators, growth factors and proteinases, resulting in enhanced cartilage degeneration and osteophyte formation. Furthermore, macrophage infiltration and soluble macrophage products may be associated with pain in OA, although data are somewhat controversial. OA synovium features macrophage heterogeneity, represented by the presence of subsets covering the broad spectrum of M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotypes, whose emergence corresponds to the cytokine profile found in OA patients. Conflicting results have been reported in both early and advanced OA concerning macrophage number, location, marker expression and cytokine profile, which may also be a consequence of the lack of universal definitions of disease stages and OA phenotypes. In this review, we summarize and discuss the positioning of synovial macrophages in knee OA in the context of pathogenesis, synovitis, and disease monitoring and as a target for therapeutic interventions.

Infrapatellar fat pad adipose tissue-derived macrophages display a predominant CD11c+CD206+ phenotype and express genotypes attributable to key features of OA pathogenesis

“…Macrophages are predominant immune cells that infiltrate IPFPs and synovial tissues of OA patients ( 7 – 11 , 26 , 27 ). They are highly plastic cells that undergo polarization in response to altered environmental stimuli or pathological conditions ( 11 , 15 ). Many diseases describe macrophages in terms of their M1 vs. M2 polarization.…”

“…Macrophages are a predominant component of mononuclear cell infiltration in synovial tissues and IPFPs and are highly activated in OA ( 7 – 9 ). Previous research has revealed the correlation between synovial macrophages with several OA pathologies ( 10 , 11 ). A high percentage of synovial macrophages was detected in the synovial tissues of OA patients with moderate-grade synovitis, suggesting the association between macrophages with synovitis ( 12 ).…”

Regenerative medicine: potential applications for foot and ankle disorders

“…Synovial-released inflammatory substances can inhibit the chondro-genetic differentiation of MSCs in cartilages, and this is probably related to an excessive prevalence of M1-like macrophages in the lesion [69][70][71][72][73][74] . The modulation of macrophage polarization towards an anti-inflammatory M2 phenotype is of vital importance in the development of regenerative cell therapies for cartilages [74][75][76][77] .…”

From Low-Grade Inflammation in Osteoarthritis to Neuropsychiatric Sequelae: A Narrative Review

“…Currently, the contribution of chronic, low-grade inflammation (Figure 1) to the development of OA and the action of inflamed synovium as a trigger of the OA process has been suggested [25,[29][30][31]. The synovial intimal cells are essential producers of various pro-inflammatory cytokines that drive the OA process in the affected joint [32][33][34][35]. Furthermore, these inflammatory mediators may activate their corresponding receptors on different brain cells and initiate various pathways of molecular signaling in the CNS [36].…”