The fibroblast expression of RANKL in CoCrMo-particle-induced osteolysis is mediated by ER stress and XBP1s

Wang, Zhenheng; Huang, Zhen; Gan, Jingjing; Liu, Naicheng; Zhou, Gang; Shi, Tongguo; Wang, Zhenzhen; Wang, Rui; Bao, Nirong; Guo, Tao; Chen, Jiangning; Zhang, Junfeng; Dong, Lei; Zhao, Jianning

doi:10.1016/j.actbio.2015.06.024

Cited by 24 publications

(18 citation statements)

References 56 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Modulating the phosphorylated level of eIF2α can promote osteogenesis and accelerate healing in vivo by activating the UPR through the PERK‐eIF2 α ‐ATF4 pathway (Figure 5). In addition, salubrinal can also promote osteogenesis and reduce osteoclast through the indirect effect on fibroblast and myoblasts, and then accelerate bone healing 40,41 . After using salubrinal, the levels of p‐eIF2α/eIF2α increased, confirming that the dephosphorylation of eIF2α was blocked, initiating the UPR reaction and adjusting intracellular stress, which plays a critical role in the responses to ER stress‐induced cell injury but is inconsistent with the results of in vitro experiments.…”

Section: Discussionmentioning

confidence: 90%

Endoplasmic reticulum stress remodels alveolar bone formation after tooth extraction

Chen

Guo

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 90%

Endoplasmic reticulum stress remodels alveolar bone formation after tooth extraction

Chen

Guo

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Based on previous studies concerning inflammatory cytokines and bone metabolism and the observation that both TiPs and CoPs were able to stimulate the production of TNF-α and IL-1β in this study, it was reasonable to speculate that TNF-α and IL-1β, produced by macrophages after the stimulation of metal nanoparticles, mediated the balance between bone resorption and formation in the pathological process of aseptic loosening ( Figure S2). 4,[34][35][36][37][38][39] SIRT1 is an important HDAC due to its proposed role in the association between calorie restriction and lifespan extension. SIRT1 is also a major regulator of bone mass.…”

Section: Discussionmentioning

confidence: 99%

The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-κB deacetylation in aseptic loosening

Deng¹,

Jin²,

Wang³

et al. 2017

IJN

Self Cite

View full text Add to dashboard Cite

Aseptic loosening is the most common cause of total hip arthroplasty (THA) failure, and osteolysis induced by wear particles plays a major role in aseptic loosening. Various pathways in multiple cell types contribute to the pathogenesis of osteolysis, but the role of Sirtuin 1 (SIRT1), which can regulate inflammatory responses through its deacetylation, has never been investigated. We hypothesized that the downregulation of SIRT1 in macrophages induced by metal nanoparticles was one of the reasons for osteolysis in THA failure. In this study, the expression of SIRT1 was examined in macrophages stimulated with metal nanoparticles from materials used in prosthetics and in specimens from patients suffering from aseptic loosening. To address whether SIRT1 downregulation triggers these inflammatory responses, the effects of the SIRT1 activator resveratrol on the expression of inflammatory cytokines in metal nanoparticle-stimulated macrophages were tested. The results demonstrated that SIRT1 expression was significantly downregulated in metal nanoparticle-stimulated macrophages and clinical specimens of prosthesis loosening. Pharmacological activation of SIRT1 dramatically reduced the particle-induced expression of inflammatory cytokines in vitro and osteolysis in vivo. Furthermore, SIRT1 regulated particle-induced inflammatory responses through nuclear factor kappa B (NF-κB) acetylation. Thus, the results of this study suggest that SIRT1 plays a key role in metal nanoparticle-induced inflammatory responses and that targeting the SIRT1 pathway may lead to novel therapeutic approaches for the treatment of aseptic prosthesis loosening.

show abstract

“…Fibroblasts secrete RANKL and promote osteoclast formation when stimulated by titanium particles 35 . Several studies have highlighted the importance of RANKL in osteolysis 7 , 36 , 37 .…”

Section: Discussionmentioning

confidence: 99%

“…Wear debris that separate from the surface of prostheses is a primary contributor to aseptic loosening 7 , 8 . Current bearing surface materials for THA have four main combinations including metal-on-polyethylene (MoP), ceramic-on-polyethylene, ceramic-on-ceramic (CoC), and metal-on-metal (MoM), of which MoP implants have been the most widely used for over 40 years.…”

Section: Introductionmentioning

confidence: 99%

Nano-sized Al2O3 particle-induced autophagy reduces osteolysis in aseptic loosening of total hip arthroplasty by negative feedback regulation of RANKL expression in fibroblasts

Wang

et al. 2018

Cell Death Dis

View full text Add to dashboard Cite

Aseptic loosening is mainly caused by wear debris generated by friction that can increase the expression of receptor activation of nuclear factor (NF)-κB (RANKL). RANKL has been shown to support the differentiation and maturation of osteoclasts. Although autophagy is a key metabolic pathway for maintaining the metabolic homeostasis of cells, no study has determined whether autophagy induced by Al2O3 particles is involved in the pathogenesis of aseptic loosening. The aim of this study was to evaluate RANKL levels in patients experiencing aseptic loosening after total hip arthroplasty (THA) and hip osteoarthritis (hOA) and to consequently clarify the relationship between RANKL and LC3II expression. We determined the levels of RANKL and autophagy in fibroblasts treated with Al2O3 particles in vitro while using shBECN-1 interference lentivirus vectors to block the autophagy pathway and BECN-1 overexpression lentivirus vectors to promote autophagy. We established a novel rat model of femoral head replacement and analyzed the effects of Al2O3 particles on autophagy levels and RANKL expression in synovial tissues in vivo. The RANKL levels in the revision total hip arthroplasty (rTHA) group were higher than those in the hOA group. In patients with rTHA with a ceramic interface, LC3II expression was high, whereas RANKL expression was low. The in vitro results showed that Al2O3 particles promoted fibroblast autophagy in a time- and dose-dependent manner and that RANKL expression was negatively correlated with autophagy. The in vivo results further confirmed these findings. Al2O3 particles induced fibroblast autophagy, which reduced RANKL expression. Decreasing the autophagy level promoted osteolysis and aseptic prosthetic loosening, whereas increasing the autophagy level reversed this trend.

show abstract

The fibroblast expression of RANKL in CoCrMo-particle-induced osteolysis is mediated by ER stress and XBP1s

Cited by 24 publications

References 56 publications

Endoplasmic reticulum stress remodels alveolar bone formation after tooth extraction

Endoplasmic reticulum stress remodels alveolar bone formation after tooth extraction

The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-κB deacetylation in aseptic loosening

Nano-sized Al2O3 particle-induced autophagy reduces osteolysis in aseptic loosening of total hip arthroplasty by negative feedback regulation of RANKL expression in fibroblasts

Contact Info

Product

Resources

About

The fibroblast expression of RANKL in CoCrMo-particle-induced osteolysis is mediated by ER stress and XBP1s

Cited by 24 publications

References 56 publications

Endoplasmic reticulum stress remodels alveolar bone formation after tooth extraction

Endoplasmic reticulum stress remodels alveolar bone formation after tooth extraction

The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-&kappa;B deacetylation in aseptic loosening

Nano-sized Al2O3 particle-induced autophagy reduces osteolysis in aseptic loosening of total hip arthroplasty by negative feedback regulation of RANKL expression in fibroblasts

Contact Info

Product

Resources

About

The metal nanoparticle-induced inflammatory response is regulated by SIRT1 through NF-κB deacetylation in aseptic loosening