BMP ‐7 ameliorates cobalt alloy particle‐induced inflammation by suppressing Th17 responses

Metal wear debris has been shown to activate an aseptic osteolytic process that causes failure in total joint arthroplasty (TJA). This osteolysis is characterized by a proinflammatory, self‐propagating immune response involving primarily macrophages, dendritic cells, and activated osteoclasts, as well as T cells and B cells. The human bone morphogenic protein (BMP)‐7, on the other hand, was shown to promote osteoblast survival, and reversed the downregulation of anabolic Smad proteins and Runx2 following cobalt injury. Therefore, we investigated the effect and mechanism of BMP‐7 on the proinflammatory immune responses in osteoarthritis patients with previous TJA. Cobalt‐treated monocytes/macrophages presented significantly elevated levels of interleukin 6 (IL‐6) and tumor necrosis factor (TNF), both of which were suppressed by the addition of exogenous BMP‐7. In patients with TJA, the serum BMP‐7 level was inversely associated with the level of IL‐6 and TNF secreted by monocytes/macrophages. Cobalt‐treated monocytes/macrophages effectively supported Th17 inflammation, by an IL‐6‐dependent but not TNF‐dependent mechanism. BMP‐7, however, significantly suppressed cobalt‐induced Th17 inflammation. In patients with TJA, the risk of osteolysis development was positively associated with the frequency of Th17 cells and negatively associated with the level of BMP‐7. Together, these results demonstrated that BMP‐7 could serve as a therapeutic agent in t...
Source: APMIS - Category: Research Authors: Tags: Original Article Source Type: research