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

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 (H2 S), the third gasotransmitter, is a critical player regulating inflammation. However, the role and therapeutic potential of H2 S in wear debris-induced inflammation and osteolysis remains to be defined. In the present study, we investigated the effect of H2 S on wear debris-induced pro-inflammatory cytokines expression and osteolysis in vitro and in vivo. With a slow-releasing H2 S donor GYY4137, our study demonstrated that H2 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 H2 S production (via H2 S donors) may represent a potential approach for the treatment of wear particle-induced osteolysis.

• Authors: Lei Liu, Ming Zhou, Ruofu Zhu, Jun Zhou, Li Ni, Zhidong Wang, Naicheng Liu, Feng Zhu, Tongguo Shi, Zhantao Deng, Yong Wang, Yixing Tian, Rongqun Li, Huilin Yang, Zhenheng Wang, Jiannong Jiang, Yaozeng Xu
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 34 Issue 3 Pg. 3743-3754 (03 2020) ISSN: 1530-6860 [Electronic] United States
• PMID: 31943384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Federation of American Societies for Experimental Biology.

Chemical References

• Sirtuin 1
• Hydrogen Sulfide

Topics

• Animals
• Blotting, Western
• Cell Survival (drug effects)
• Enzyme-Linked Immunosorbent Assay
• Fluorescent Antibody Technique
• Hydrogen Sulfide (therapeutic use)
• Inflammation (drug therapy, metabolism)
• Mice
• Osteolysis (drug therapy, metabolism)
• RAW 264.7 Cells
• Real-Time Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Sirtuin 1 (metabolism)
• X-Ray Microtomography