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 (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.

Astaxanthin ameliorates oxidative stress and neuronal apoptosis via SIRT1/NRF2/Prx2/ASK1/p38 after traumatic brain injury in mice

“…SIRT1 might be involved in the mechanisms by which astaxanthin modulates Nrf2/Prx2/ASK1/p38 signalling after traumatic brain injury. SIRT1 is a type of histone deacetylase that regulates a variety of cellular biochemical processes (Li et al, 2020; Liu et al, 2020; Wu et al, 2018; Zhang, Bi, et al, 2019). Mounting evidence indicated that SIRT1 could enhance the expression and transcriptional activity of Nrf2 to exert potent anti‐oxidant effects (Huang et al, 2013).…”

Resveratrol‐enhanced SIRT1‐mediated osteogenesis in porous endplates attenuates low back pain and anxiety behaviors

“…Under various internal and external conditions, the enhanced expression of SIRT1 in mesenchymal stem cells promotes osteogenic differentiation 17 and protects against bone loss 18 . Correspondingly, the downregulation of SIRT1 promotes osteoclastogenesis and osteolysis in mice 46,47 . To verify whether resveratrol‐mediated analgesic effect through the activation of SIRT1‐triggered osteogenesis in the porous endplates, the SIRT1 OSX −/− mice were employed.…”

The Effects of Biomaterial Implant Wear Debris on Osteoblasts

“…In vitro pharmacological up-regulation and activation of SIRT1 with resveratrol ameliorated the particle-induced osteoblastic apoptosis and inflammatory cytokine expression by suppressing SIRT1-p53 and SIRT1-NF-κB signaling, respectively. Unsurprisingly, in vivo SIRT1 activation by resveratrol and GYY4137 protected cells from osteoblast dysfunction, attenuated particle-induced inflammatory responses, and osteolysis in PIO mouse models (Deng et al, 2017b;Liu et al, 2020).…”