Regulation of osteoclastogenesis by mast cell in rheumatoid arthritis

Abstract

Background In the pathogenesis of rheumatoid arthritis (RA), the role of mast cells has not been revealed clearly. We aimed to define the inflammatory and tissue-destructive roles of mast cells in rheumatoid arthritis (RA). Methods Serum and synovial fluid (SF) concentration levels of tryptase, chymase, and histamine were quantified using ELISA. After activating mast cells using IL-33, the production of TNF-α, IL-1β, IL-6, IL-17, RANKL, and MMPs was determined using real-time PCR and ELISA. Osteoclastogenesis was assessed in CD14+ monocytes from peripheral blood and SF, which were cultured with IL-33-activated mast cells, by counting TRAP-positive multinucleated cells. Results The concentration levels of serum tryptase, chymase, and histamine and SF histamine were higher in patients with RA than in controls. FcεR1 and c-kit-positive mast cells were higher in RA synovium than in osteoarthritic (OA) synovium. Stimulation of mast cells by IL-33 increased the number of trypatse+chymase− and tryptase+chymase+ mast cells. IL-33 stimulation also increased the gene expression levels of TNF-α, IL-1β, IL-6, IL-17, RANKL, and MMP-9 in mast cells. Furthermore, IL-33 stimulated human CD14+ monocytes to differentiate into TRAP+ multinucleated osteoclasts. When CD14+ monocytes were co-cultured with mast cells, osteoclast differentiation was increased. Additionally, IL-33-activated mast cells stimulated osteoclast differentiation. The inhibition of intercellular contact between mast cells and monocytes using inserts reduced osteoclast differentiation. Conclusions IL-33 increased inflammatory and tissue-destructive cytokines by activation of mast cells. Mast cells stimulated osteoclast differentiation in monocytes. Mast cells could stimulate osteoclastogenesis indirectly through production of tissue-destructive cytokines and directly through stimulation of osteoclast precursors.

Dimethylamino group modified polydopamine nanoparticles with positive charges to scavenge cell-free DNA for rheumatoid arthritis therapy

“…In synovial tissues, lymphocytes and synoviocytes produced excessive inflammatory cytokines, such as IL-6, IL-1β and TNF-α, leading to synovitis [ 47 ]. Furthermore, cytokine stimulated synoviocytes secreted MMP and receptor activator of nuclear factor kappa B ligand (RANKL) into SF and consequently lead to cartilage degradation and joint destruction [ 48 ]. The pathobiology progression of CIA rat model was similar to that in RA patients.…”

Mast Cells Trigger Disturbed Bone Healing in Osteoporotic Mice

“…( 15 ) The results of the present study indicate for the first time that mast cells’ osteoclastogenic effects might also be mediated partly via RANKL. Indeed, mast cells were shown to release RANKL in the inflammatory conditions of atherosclerosis or rheumatoid arthritis ( 3,71 ) and after bone fracture. ( 15 )…”

“…(15) The results of the present study indicate for the first time that mast cells' osteoclastogenic effects might also be mediated partly via RANKL. Indeed, mast cells were shown to release RANKL in the inflammatory conditions of atherosclerosis or rheumatoid arthritis (3,71) and after bone fracture. (15) In the present study, we aimed to investigate the cross-talk between mast cells and osteoclasts in more detail and with more translational relevance.…”

Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications

“…MCs can also participate in bone destruction by promoting the release of proteases, histamine, TNF-a, IL-6, IL-11, IFN-g, RANKL, and other mediators. MCs increase the expression level of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMP-9 genes in response to IL-33 stimulation and stimulate human CD14+ monocytes to differentiate into TRAP-positive osteoclasts (83). Shin et al found that secretion of tryptase b by MCs was abundant in experimental models of arthritic mice, and the tryptase b/ heparin complex promoted FLS to express inflammationmediating neutrophil chemokines CXCL1/KC, CXCL5/LIX, and CXCL8/IL-8; additionally, tryptase b-deficient mice showed lower disease activity and bone destruction (84).…”