Hydrogen sulfide protects against particle‐induced inflammatory response and osteolysis via SIRT1 pathway in prosthesis loosening

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Abstract
Wear debris‐induced osteolysis and ensuing aseptic loosening is the main cause of implant failure and revision surgery. Wear debris‐induced inflammatory response plays key roles in peri‐implant osteolysis. Recently, substantial of evidence suggests that hydrogen sulfide (H 2 S), the third gasotransmitter, is a critical player regulating inflammation. However, the role and therapeutic potential of H 2 S in wear debris‐induced inflammation and osteolysis remains to be defined. In the present study, we investigated the effect of H 2 S on wear debris‐induced pro‐inflammatory cytokines expression and osteolysis in vitro and in vivo. With a slow‐releasing H 2 S donor GYY4137, our study demonstrated that H 2 S attenuated wear debris‐induced osteolysis and osteoclastogenesis in murine calvaria resorption models. The expression of tumor necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6) that stimulated by wear particles were significantly reduced by GYY4137. Further, the level of sirtuin 1 (SIRT1), which possesses anti‐inflammation property, was examined in vivo and in macrophages. And we found that wear debris decreased the expression of SIRT1. Cotreated macrophages with GYY4137 in part reversed the decline of SIRT1. More importantly, with the SIRT1 recombinant lentivirus and small interfering RNAs (siRNA) against SIRT1, our data indicated that SIRT1 mediated the inhibitory effects of GYY4137 on wear debris‐induced inflammation. Collectively, these results suggested that exogenous H 2 S production (via H 2 S donors) may represent a potential approach for the treatment of wear particle‐induced osteolysis.
Funding Information
  • National Natural Science Foundation of China (81802223,81702214,81802843,81802222,81572111,81772318)

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