Abstract

This study aims to investigate the effect of enriched plasma cells on the production of inflammatory cytokines and development of osteoarthritis (OA) in mice with B-cell-specific conditional deletion of the tuberous sclerosis 1 gene (TSC1). OA was induced by destabilization of the medial meniscus (DMM) in mice with TSC1 disruption in B cells (CD19-TSC1) and in littermate control mice (CON). The effects of DMM and incidence of OA were evaluated histologically, mRNA levels of inflammatory cytokines were detected by polymerase chain reaction, and serum cytokine levels were detected by enzyme-linked immunosorbent assay. Deletion of TSC1 caused constitutive activation of mechanistic target of rapamycin complex 1 mTORC1 in B cells. CON mice subjected to DMM exhibited a severe OA phenotype with increased inflammatory cytokines in B cells, serum, and the synovial membrane. Importantly, inflammatory cytokine production was also increased in B cells from the spleen of CD19-TSC1 conditional KO mice, but the OA phenotype was significantly elevated in conditional KO mice after DMM surgery compared with CON mice, as indicated by more severe articular cartilage destruction, increased protein expression of matrix metalloproteinase-13 and mRNA of type X collagen in the articular cartilage, decreased mRNA expression of type II collagen in the articular cartilage, and increased inflammatory cytokines in serum and the synovial membrane. The results demonstrate that inflammatory cytokine synthesis by B cells was enriched in CD19-TSC1 conditional KO mice, and this enhanced synthesis of inflammatory cytokines accelerated the incidence of OA.

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