The multifaceted role of mast cells in joint inflammation and arthritis.

Objective: To review current knowledge surrounding the role of mast cells in joint inflammation and arthritis.

Method: Narrative review.

Results: Mast cells (MCs) are commonly observed in the synovium of the joint, particularly surrounding blood vessels and nerve endings. Some studies have reported increased MC number and degranulation in patients with osteoarthritis (OA). In two studies, MCs were the only immune cell type found in higher concentrations in synovium of OA patients compared to rheumatoid arthritis patients. Activation of MCs in OA includes signaling pathways such as immunoglobulin E/Fc epsilon Receptor 1 (IgE/FcεR1), immunoglobulin G/Fc gamma receptor (IgG/FcγR), complement, and toll-like cell surface receptor-mediated signaling, resulting in context-dependent release of either pro-inflammatory and/or anti-inflammatory mediators within the joint. Activation of MCs results in the release of pro-inflammatory mediators that ultimately contribute to inflammation of the synovium, bone remodeling, and cartilage damage. However, some studies have proposed that MCs can also exhibit anti-inflammatory effects by secreting mediators that inactivate pro-inflammatory cytokines such as interleukin 6 (IL-6).

Conclusions: MCs may play a role in mediating synovial inflammation and OA progression. However, the mechanisms governing MC activation, the downstream pro- and/or anti-inflammatory effects, and their impact on osteoarthritis pathogenesis remains to be elucidated and requires extensive further study. Furthermore, it is important to establish the pathways of MC activation in OA to determine whether MCs exhibit varying phenotypes as a function of disease stage. Ultimately, such research is needed before understanding whether MCs could be targeted in OA treatments.