Effects of synovial macrophages in osteoarthritis

Abstract

Osteoarthritis (OA) is a common degenerative disease in mammals. However, its pathogenesis remains unclear. Studies indicate that OA is not only an aging process that but also an inflammation-related disease. Synovitis is closely related to the progression of OA, and synovial macrophages are crucial participants in synovitis. Instead of being a homogeneous population, macrophages are polarized into M1 or M2 subtypes in OA synovial tissues. Polarization is highly associated with OA severity. However, the M1/M2 ratio cannot be the only factor in OA prognosis because intermediate stages of macrophages also exist. To better understand the mechanism of this heterogeneous disease, OA subtypes of synovial macrophages classified by gene expression were examined. Synovial macrophages do not act alone; they interact with surrounding cells such as synovial fibroblasts, osteoclasts, chondrocytes, lymphocytes and even adipose cells through a paracrine approach to exacerbate OA. Treatments targeting synovial macrophages and their polarization are effective in relieving pain and protecting cartilage during OA development. In this review, we describe how synovial macrophages and their different polarization states influence the progression of OA. We summarize the current knowledge of the interactions between macrophages and other joint cells and examine the current research on new medications targeting synovial macrophages.

Nanomedicines Promote Cartilage Regeneration in Osteoarthritis by Synergistically Enhancing Chondrogenesis of Mesenchymal Stem Cells and Regulating Inflammatory Environment

“…As reported, M1 macrophages primarily produced proinflammatory cytokines and are closely related to synovial inflammation in OA. , To evaluate the anti-inflammatory effects of AHK-CaP/siCA9 NPs, the levels of major inflammatory cytokines secreted from LPS-activated RAW 264.7 cells were detected using ELISA kits. Compared with the NT group, the control group markedly increased the levels of TNF-α (∼1.7-fold) and IL-6 (∼2-fold), indicating the production of inflammatory microenvironment induced by LPS-activated M1 macrophages (Figure G-H).…”

M2 Macrophage-Derived Extracellular Vesicles Encapsulated in Hyaluronic Acid Alleviate Osteoarthritis by Modulating Macrophage Polarization

“…Synovial macrophages respond to their microenvironment by differentiating into two main subtypes, M1 and M2 type macrophages. 3 M1 macrophages stimulated by lipopolysaccharide (LPS) have proinflammatory effects and are characterized by the expression of CD86, inducible nitric oxide synthase (iNOS), and the secretion of proinflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor α (TNF-α). 4 In contrast, M2 macrophages stimulated by IL-4 have anti-inflammatory effects and are characterized by the expression of arginase (ARG)-1 and CD206.…”

“…Synovitis is characterized by synovial lining hyperplasia, new blood vessel formation, and lymphocyte and macrophage infiltration, which accelerate cartilage loss and is accompanied by joint pain and impaired mobility . Growing evidence suggests that macrophages play an important role in low-grade OA-related inflammation . However, the specific role and underlying mechanism of macrophages in OA development are not clear.…”

“…2 Growing evidence suggests that macrophages play an important role in low-grade OA-related inflammation. 3 However, the specific role and underlying mechanism of macrophages in OA development are not clear.…”

The role of monocyte/macrophage chemokines in pathogenesis of osteoarthritis: A review

“…Macrophages can interact directly with synovial fibroblasts (SFs) and chondrocytes to promote the secretion of pro-inflammatory factors and cartilage-degrading mediators, mediating synovitis and cartilage degeneration (Zhao et al, 2023). Macrophage-derived osteoclasts are overactivated in OA, regulating subchondral bone destruction and bone resorption (Adamopoulos et al, 2006).…”