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

• Published in: The FASEB journal 2020-03, Vol.34 (3), p.3743-3754
• Main Authors: Liu, Lei, Zhou, Ming, Zhu, Ruofu, Zhou, Jun, Ni, Li, Wang, Zhidong, Liu, Naicheng, Zhu, Feng, Shi, Tongguo, Deng, Zhantao, Wang, Yong, Tian, Yixing, Li, Rongqun, Yang, Huilin, Wang, Zhenheng, Jiang, Jiannong, Xu, Yaozeng
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Cell Survival - drug effects; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; GYY4137; hydrogen sulfide; Hydrogen Sulfide - therapeutic use; inflammation; Inflammation - drug therapy; Inflammation - metabolism; Mice; Osteolysis - drug therapy; Osteolysis - metabolism; RAW 264.7 Cells; Real-Time Polymerase Chain Reaction; Signal Transduction - drug effects; SIRT1; Sirtuin 1 - metabolism; wear particles; X-Ray Microtomography
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201900393RR

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 (H2S), the third gasotransmitter, is a critical player regulating inflammation. However, the role and therapeutic potential of H2S in wear debris‐induced inflammation and osteolysis remains to be defined. In the present study, we investigated the effect of H2S on wear debris‐induced pro‐inflammatory cytokines expression and osteolysis in vitro and in vivo. With a slow‐releasing H2S donor GYY4137, our study demonstrated that H2S 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 H2S production (via H2S donors) may represent a potential approach for the treatment of wear particle‐induced osteolysis.