Irisin recouples osteogenesis and osteoclastogenesis to protect wear-particle-induced osteolysis by suppressing oxidative stress and RANKL production

Hu, Sihan; Xue, Yadong; He, Jiachen; Chen, Chichi; Sun, Jie; Jin, Yesheng; Zhang, Yuanshu; Shi, Qin; Rui, Yongjun

doi:10.1039/d1bm00563d

Cited by 18 publications

(12 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the clinical relevance of the murine calvaria model should be considered with caution. Besides, although our in vitro studies protocols are similar to previous studies ( Qiu et al, 2020 ; Hu et al, 2021 ) concerning the wear particles-induced inflammation and osteolysis, we must admit that future cell studies with a longer stimulation time are needed to further investigate the protective effect of ICA on chronic inflammatory reactions caused by wear particles.…”

Section: Discussionmentioning

confidence: 97%

Icariin Alleviates Wear Particle-Induced Periprosthetic Osteolysis via Down-Regulation of the Estrogen Receptor α-mediated NF-κB Signaling Pathway in Macrophages

Wen

Deng

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Periprosthetic osteolysis is one of the major long-term complications following total joint replacement. Its cause is widely accepted to be wear particle-induced activation of inflammatory macrophages. No effective strategy for the prevention and treatment of periprosthetic osteolysis is yet available. Recently, considerable evidence has shown that icariin effectively protects against estrogen deficiency-related bone loss and bone deterioration. However, the molecular mechanism underlying the inhibitory effect of icariin on wear particle-induced periprosthetic osteolysis is not yet clear. In this study, nanoscale CoCrMo wear particles were obtained by high-vacuum three-electrode direct current from the femoral head implant of a patient diagnosed with aseptic loosening. The effects of icariin on wear particle-induced expression of proinflammatory factors, NF-κB signaling modulation, osteolysis, and estrogen receptor α (ERα) activation were evaluated in vitro and in vivo using bone marrow-derived macrophages and C57/BL6J mice, respectively. A possible link between ERα and the protective effect of icariin was further studied using an ERα antagonist and the ERα-siRNA interference. Chemical composition analysis showed that Cr and Co were the major metallic elements of the nanoscale particles, with a mean size of 150.2 ± 37.4 nm for the CoCrMo particles. Following icariin treatment, significant decreases were observed in CoCrMo wear particle-induced TNF-α and IL-6 mRNA expression in BMDMs, and osteolysis in mice calvaria. Marked decreases in the protein expression level of p-IKKβ, p-p65 and p-IκBα were also observed, together with significant decreases in the nuclear import of P65 and macrophage M1 polarization. RNA sequencing revealed that ERα was closely associated with TNF-α and IL-6 in wear particle-stimulated macrophages. Furthermore, marked increases in phospho-ERα Ser118 and phospho-ERα Ser167 protein expression and the nuclear import of ERα were also found in the icariin group. The protective effects of icariin on CoCrMo particle-induced mouse calvarial osteolysis and on the inflammation response in BMDMs were reversed by ERα antagonist and by ERα-siRNA interference. In conclusion, icariin attenuates wear particle-induced inflammation and osteolysis via down-regulation of the ERα-mediated NF-κB signaling pathway in macrophages. The potential application of icariin as a non-hormonal therapy for wear particle-induced periprosthetic osteolysis is worthy of further investigation.

show abstract

Section: Discussionmentioning

confidence: 97%

Icariin Alleviates Wear Particle-Induced Periprosthetic Osteolysis via Down-Regulation of the Estrogen Receptor α-mediated NF-κB Signaling Pathway in Macrophages

Wen

Deng

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Thus, regulating excessive ROS production and osteoclastogenesis can be a strategy to treat PPO. Hu et al revealed that suppressing ROS and RANKL production protected against osteolysis [ 43 ]. Sun et al developed a few-layered Nb2C (FNC) as an antioxidant to scavenge ROS and inhibit osteoclastogenesis to attenuate osteolysis [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway

et al. 2022

View full text Add to dashboard Cite

Periprosthetic osteolysis (PPO) triggered by wear particles is the most severe complication of total joint replacement (TJR) surgeries, representing the major cause of implant failure, which is public health concern worldwide. Previous studies have confirmed the specialized role of osteoclast-induced progressive bone destruction in the progression of PPO. Additionally, the reactive oxygen species (ROS) induced by wear particles can promote excessive osteoclastogenesis and bone resorption. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), a cellular enzyme, is considered to be responsible for the production of ROS and the formation of mature osteoclasts. However, NOX4 involvement in PPO has not yet been elucidated. Therefore, we investigated the mechanism by which NOX4 regulates osteoclast differentiation and the therapeutic effects on titanium nanoparticle-induced bone destruction. We found that NOX4 blockade suppressed osteoclastogenesis and enhanced the scavenging of intracellular ROS. Our rescue experiment revealed that nuclear factor-erythroid 2-related factor 2 (Nrf2) silencing reversed the effects of NOX4 blockade on ROS production and osteoclast differentiation. In addition, we found increased expression levels of NOX4 in PPO tissues, while NOX4 inhibition in vivo exerted protective effects on titanium nanoparticle-induced osteolysis through antiosteoclastic and antioxidant effects. Collectively, these findings suggested that NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway and that NOX4 blockade may be an attractive therapeutic approach for preventing PPO. Graphical Abstract

show abstract

“…The conditioned medium was prepared according to previously published methods with a little modification. 28 Briefly, RAW 264.7 cells were seeded in 60 mm culture dishes at a density of 1.0 × 10 5 cells per well.…”

Section: Intracellular Ros Scavenging Experiments and Peroxidative Pr...mentioning

confidence: 99%

Bimetallic Metal–Organic Framework for Mitigating Aseptic Osteolysis

Pan

Miao

Deng

et al. 2023

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

The disability rate of joint diseases can be reduced by the use of artificial joints, but joint loosening at a late state limits the lifespan and surgical efficacy of the joints. Wear particles can be recognized by macrophages and induce cells to produce reactive oxygen species (ROS) and inflammatory factors, causing persistent inflammation and decreased osteogenic activity, which ultimately leads to loosening of joint prostheses. Here, the platinum (Pt) nanozymes with excellent ROS scavenging and anti-inflammatory capabilities were encapsulated in zinc imidazolium zeolite framework-8 (ZIF-8), and then the osteogenic active element lanthanum (La) was introduced through ion exchange to finally construct a bimetallic metal−organic framework (Pt@ZIF-8@ La). In vitro and in vivo experiments demonstrated that this multifunctional nanoplatform possessed the functions of efficient scavenging of ROS, immune regulation, and promotion of osteogenic differentiation. Meanwhile, the mechanism is explored that Pt@ZIF-8@La can also promote osteogenic mineralization by upregulating the ratio of the osteoprotegerin (OPG)/receptor activator of the NF-κB ligand (RANKL), which can achieve a synergistic therapeutic effect of immunomodulation and osteogenesis, thereby realizing the purpose of relieving aseptic osteolysis.

show abstract

Irisin recouples osteogenesis and osteoclastogenesis to protect wear-particle-induced osteolysis by suppressing oxidative stress and RANKL production

Abstract: Disruption of bone homeostasis with the decrease of osteoblastic bone formation and the facilitated osteoclastic bone resorption is the leading cause of periprosthetic osteolysis. Accumulative studies indicate irisin has the...

Cited by 18 publications

References 46 publications

Icariin Alleviates Wear Particle-Induced Periprosthetic Osteolysis via Down-Regulation of the Estrogen Receptor α-mediated NF-κB Signaling Pathway in Macrophages

Icariin Alleviates Wear Particle-Induced Periprosthetic Osteolysis via Down-Regulation of the Estrogen Receptor α-mediated NF-κB Signaling Pathway in Macrophages

NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway

Bimetallic Metal–Organic Framework for Mitigating Aseptic Osteolysis

Contact Info

Product

Resources

About