Macrophages regulate the progression of osteoarthritis

Abstract

OA is now well accepted as a low-grade inflammatory disease affecting the whole joint. In addition to mechanical loading, inflammation (particularly synovitis), contributes significantly to OA. Synovial macrophages act as immune cells and are of critical importance in the symptomology and structural progression of OA. Activated macrophages are regulated by mTOR, NF-kB, JNK, PI3K/Akt and other signaling pathways, and are polarized into either M1 or M2 subtypes in OA synovial tissues, synovial fluid, and peripheral blood. The activation state and the M1/M2 ratio is highly associated with OA severity. Aside from autocrine interactions, paracrine interactions between macrophages and chondrocytes play a vital role in the initiation and development of OA by secreting inflammatory cytokines, growth factors, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs), which lead to subsequent cartilage degradation and destruction. Treatments targeting synovial macrophages relieve pain, and protect from synovitis, cartilage damage, and osteophyte formation during OA development. Macrophage reprogramming of transformation from the M1 to M2 subtype, more than a decrease in the quantity of activated macrophages, appears to be an effective treatment option for OA. This review provides a broad understanding of the contributions of polarized macrophages to joint health and disease. Multifunctional agents with immunomodulatory effects on macrophage reprogramming can skew the inflammatory microenvironment towards a pro-chondrogenic atmosphere, and are thus, potential therapeutic options for the treatment of OA and other immune diseases.

Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways

“…Monocyte adhesion to synovium tissue is an important phenomenon in OA pathogenesis [ 28 ]. However, nothing is known about the impact of resistin-enhanced VCAM expression and monocyte adhesion to synovium tissue in OA pathogenesis.…”

Biomarkers of Joint Damage in Osteoarthritis: Current Status and Future Directions

“…Macrophages activate an innate immune response in OA pathology and progression. Thus, the products of macrophages play a role in OA pathology and can be used to understand OA mechanism and therapeutic innovations [66].…”

Clinical-grade hDPSCs Suppressed the Activation of Osteoarthritic Macrophages and Attenuated Cartilaginous Damage in a Rabbit OA Model

“…Macrophages are hematopoietic stem cell-derived immune cells and have now been shown to play a prominent role in the progression of OA. Increasing evidence has demonstrated that overactivated macrophages promote the in ammatory microenvironment, increase the secretion of matrix metalloproteinases, inhibit the proliferation and viability of joint resident stem cells, and prevent cartilage repair [9][10][11]. Haraden et al reported that osteoarthritic macrophages highly expressed costimulatory factors such CD80 and CD86, which further initiated the adaptive immune response and induced expanded tissue injury [11,12].…”