Expression of XBP1s in fibroblasts is critical for TiAl₆V₄ particle‐induced RANKL expression and osteolysis

Abstract

Wear particle-induced osteolysis is a major cause of aseptic loosening, which is one of the most common reasons for total hip arthroplasty (THA) failure. Previous studies have shown that the expression of Receptor activation of nuclear factor (NF)-kB (RANKL) by fibroblasts in periprosthetic membrane played a crucial role in wear particle-induced osteolysis. However, the underlying mechanism of RANKL expression remains largely unknown. In the present study, we investigated the effect of TiAl V particle (TiPs)-induced XBP1s (spliced form of X-box binding protein 1) on RANKL expression and osteoclastogenesis both in vitro and in vivo. The levels of XBP1s in peri-implant membrane, animal models, and TiPs-stimulated fibroblasts were determined by western blots. To assess the effect of XBP1s on RANKL expression, fibroblasts were treated with both a small interfering RNA (siRNA) and an inhibitor of XBP1 prior to exposure to TiPs. The effect of XBP1s on osteoclasts formation was determined by tartrate-resistant acid phosphatase (TRAP) staining in vitro osteoclastogenesis assay and in animal models. The resorption of bone was assessed by micro-computed tomography (micro-CT) with three-dimensional reconstruction. Our results demonstrated that XBP1s was activated in periprosthetic membrane, mouse calvaria models, and TiPs-stimulated human synovial fibroblasts. Further, inhibition of XBP1s decreased the expression of RANKL and osteoclasts formation in vitro. In mouse calvaria models, both of the osteoclastogenesis and osteolysis were inhibited XBP1s inhibitor. Our results suggested that XBP1s mediated TiPs-induced of RANKL expression in fibroblasts, and down regulating XBP1s may represent a potential therapy for wear particle-induced osteolysis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:752-759, 2017.

Bone and joint infection: past, present, and future

“…Recently, increasing evidence has suggested that as a representative of host factors, single nucleotide variations (SNVs) were also linked to PTOM development. Such SNVs included but were not limited to rs689466 in cyclooxygenase-2 (COX-2) gene (Wang et al, 2017), rs16944, rs2234663, rs1143627, rs4251961, rs1800796, and rs2234663 in interleukin (IL) genes (Alves De Souza et al, 2017;Jiang et al, 2020). These findings demonstrated that SNVs might play essential roles in PTOM development.…”

Enteropathogenic Escherichia coli Mediates CoCrMo Particle-Induced Peri-Implant Osteolysis by Increasing Peripheral 5-HT

“…However, the ratio of revision after hip arthroplasty still remains at a high level with aseptic loosening accounting for the largest part of surgical failure. Wear particles are regarded as a critical role in the pathogenesis of aseptic loosening and osteolysis by interacting with multiple cell types from the peri-implant tissue and resulting in various biological reactions ( Wang et al., 2013 ; Wang et al., 2015a ; Wang et al., 2017a ). Most studies on particle-induced osteolysis have focused on the role of local factors in mediating bone resorption and bone formation ( Deng et al., 2017b ; Liu et al., 2020 ).…”

“…(2011) suggested that Bifidobacterium can protect from EPEC infection. In addition, our previous study suggested that L. casei could reduce particle-induced osteolysis by decreasing the M1-like macrophage/M2-like macrophage ratio ( Wang et al., 2017a ). Collectively, administration of probiotic, especially EPEC-fighting strains, in aseptic loosening patients may also be a potent treatment approach.…”

“…Total RNA from calvarial bone was prepared using TRIzol reagent (15596-018, Invitrogen, Waltham, MA, USA) according to the manufacturer’s instructions. As previously described ( Wang et al., 2017a ), real-time PCR was performed using 2× SYBR Green qPCR Mix (PC01, Zoonbio Biotechnology Co., Nanjing, China) according to the manufacturer’s protocol. Primers for b-actin were used as internal controls.…”

“…Thus, there is still a lack of appropriate pharmacology prevention measures for osteolysis and aseptic loosening. Recently, our study found that Lacticaseibacillus casei , a common probiotic, could reduce particle-induced osteolysis by mediating macrophage polarization, indicating that the gut microbiota (GM) may be implicated in the progression of aseptic loosening ( Wang et al., 2017a ).…”