Tabersonine alleviates wear particle-induced inflammatory osteolysis by inhibiting osteoclast activation / 中国组织工程研究

BACKGROUND:Tabersonine has shown good therapeutic effects in diseases such as myocardial remodeling,acute kidney injury and lung injury due to its anti-inflammatory biological activity.Prosthetic wear particles often lead to aseptic inflammation,and the massive release of inflammatory factors further promotes periprosthetic bone destruction and bone loss;however,there are no basic studies on the efficacy of tabersonine on periprosthetic osteolysis. OBJECTIVE:To investigate the effects of tabersonine on osteoclast activation,expression of inflammatory factors and inflammatory osteolysis induced by wear particles. METHODS:(1)Cell experiment:RAW264.7 cells were divided into four groups for culture.A complete medium was added in the control group.Osteoclast induction medium(50 ng/mL RANKL+complete medium)was added to the osteoclast induction group.1 and 5 μmol/L tabersonine was added for 4 hours,and then osteoclast induction medium was added to the low-and high-dose tabersonine groups,respectively.After 5 days of induction,tartrate-resistant acid phosphatase staining,F-actin staining and RT-PCR were performed.(2)Animal experiments:Twenty C57BL/6J mice were randomly divided into sham operation group,osteolysis group,low-dose tabersonine group and high-dose tabersonine group(n=5 per group).Skull osteolysis model of the skull was established by injecting titanium pellets on the skull surface in the osteolysis group,low-dose tabersonine group and high-dose tabersonine group.On day 2 after model establishment,mice in the low-dose and high-dose tabersonine groups received intraperitoneal injections of 10 and 20 mg/kg tabersonine every 2 days,respectively.2 weeks after surgery,mouse sera were collected for detecting inflammatory factors(interleukin 1β,interleukin 6,and tumor necrosis factor α),and cranial bones were collected for micro-CT scan and bone parameter analysis. RESULTS AND CONCLUSION:(1)Cellular experiments:Tartrate-resistant acid phosphatase staining and F-actin staining showed that compared with the osteoclast induction group,low-dose and high-dose tabersonine significantly inhibited osteoclast activation and bone resorption,and the inhibition was more significant in the high-dose tabersonine group.RT-PCR results showed that compared with the control group,the mRNA expressions of three kinds of inflammatory factors were increased in the osteoclast induction group(P<0.01).Compared with the osteoclast induction group,the mRNA expressions of three kinds of inflammatory factors were decreased in low-and high-dose tabersonine groups(P<0.01),and the decrease was more obvious in the high-dose tabersonine group.(2)Animal experiments:Compared with the sham operation group,the levels of three kinds of inflammatory factors were increased in the osteolysis group(P<0.01).Compared with the osteolysis group,the levels of three kinds of inflammatory factors were decreased in the low-and high-dose tabersonine groups(P<0.05,P<0.01),and the decrease was more obvious in the high-dose tabersonine group.The micro-CT scan results revealed that titanium particles caused the destruction of cranial osteolysis,and tabersonine could inhibit the osteolysis induced by titanium particles,especially in the high-dose tabersonine group.(3)The results confirm that tabersonine can enhance the osteolysis and bone destruction induced by titanium particles by inhibiting the release of inflammatory factors and down-regulating the bone absorption function of osteoclasts.

Novel programmed cell death in periprosthetic osteolysis / 中国组织工程研究

BACKGROUND:In addition to apoptosis,recent studies have discovered novel forms of programmed cell death in periprosthetic osteolysis,which is involved in regulating local chronic inflammation and the outcome of osteoblast and osteoclast under pathological conditions.This has an important value for the treatment and prognosis of periprosthetic osteolysis. OBJECTIVE:To provide new ideas and strategies for the prevention and treatment of periprosthetic osteolysis by summarizing studies on the novel forms of programmed cell death. METHODS:The first author used the computer to search the articles published from 2005 to 2022.Chinese search terms"wear particles,periprosthetic osteolysis,programmed cell death,apoptosis,autophagy,pyroptosis,necrotizing apoptosis,iron death"were used to search the databases of CNKI,WanFang and VIP.English search terms"osteolysis,wear debris,wear particles,peri*prosthetic osteolysis,PPOL,aseptic loosening,autophagy,regulated cell death,programmed cell death,apoptosis,pyroptosis,autophagic cell death,autophagy,necroptosis,ferroptosis"were used for search in PubMed and Web of Science databases.A total of 68 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:(1)Inadequate or excessive activation of autophagy can cause cell death,inhibit bone formation,and promote bone resorption,leading to bone metabolism disorders and osteolysis.(2)Recent studies have paid close attention to pyroptosis in periprosthetic osteolysis,where the Nod-like receptor,pyrin containing 3 inflammasome plays an important role in local inflammation.Inhibiting pyroptosis can effectively alleviate osteolysis.(3)In vitro studies have shown that necroptosis can inhibit the formation and function of osteoblasts and osteoclasts,affecting the process of osteolysis and destruction.(4)Ferroptosis is the newest form of programmed cell death,which is regulated by complex signaling pathways and mechanisms,but is not yet fully understood.(5)Autophagy,pyroptosis,necroptosis,and ferroptosis play important roles in the development of periprosthetic osteolysis,and their associated signaling pathways and genes require further investigation.

Inhibitory Effects of Tripterine on Wear Particle-Induced Cellular Inflammatory Reaction / 天津医药

Objective To investigate the effect of tripterine on wear particle-induced inflammatory reaction by cell culture in vitro. Methods Wear particles from artificial joints were prepared by vacuum ball milling, and made into the par-ticle suspension by using serum-free medium. RAW264.7 cells were cultured, subcultured and divided randomly into four groups according to different treatment factors:blank control group (group A), wear particle group (group B), wear particle+tripterine group (group C) and tripterine group (group D). After 24 hours, the toxicity of tripterine was detected by CCK-8 as-say. ELISA was used to detect the expressions of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β). RT-PCR was used to detect the expressions of TNF-α, IL-1βand nuclear factor-κB (NF-κB) at the gene level. Western blot assay was used to detect the expression of NF-κB at the protein level. Results The results showed that 1 mg/L tripterine was little cytotoxic. The expressions of pro-inflammatory cytokines and the activation of NF-κB were significantly higher in wear particle group than those in blank control group (P＜0.05), which were significantly decreased after the treatment with tripter-ine (group C, P＜0.05). Conclusion Tripterine can inhibit the wear particle-induced expression and release of pro-inflam-matory cytokines at the gene level and protein level and the activation of NF-κB in RAW264.7 cells.

In vitro studies of multiwalled carbon nanotube/ultrahigh molecular weight polyethylene nanocomposites with osteoblast-like MG63 cells

Carbon nanotubes are highly versatile materials; new applications using them are continuously being developed. Special attention is being dedicated to the possible use of multiwalled carbon nanotubes in biomaterials contacting with bone. However, carbon nanotubes are also controversial in regards to effects exerted on living organisms. Carbon nanotubes can be used to improve the tribological properties of polymer/composite materials. Ultrahigh molecular weight polyethylene (UHMWPE) is a polymer widely used in orthopedic applications that imply wear and particle generation. We describe here the response of human osteoblast-like MG63 cells after 6 days of culture in contact with artificially generated particles from both UHMWPE polymer and multiwalled carbon nanotubes (MWCNT)/UHMWPE nanocomposites. This novel composite has superior wear behavior, having thus the potential to reduce the number of revision hip arthroplasty surgeries required by wear failure of acetabular cups and diminish particle-induced osteolysis. The results of an in vitro study of viability and proliferation and interleukin-6 (IL-6) production suggest good cytocompatibility, similar to that of conventional UHMWPE (WST-1 assay results are reported as percentage of control ± SD: UHMWPE = 96.19 ± 7.92, MWCNT/UHMWPE = 97.92 ± 8.29 percent; total protein: control = 139.73 ± 10.78, UHMWPE = 137.07 ± 6.17, MWCNT/UHMWPE = 163.29 ± 11.81 µg/mL; IL-6: control = 90.93 ± 10.30, UHMWPE = 92.52 ± 11.02, MWCNT/UHMWPE = 108.99 ± 9.90 pg/mL). Standard cell culture conditions were considered as control. These results, especially the absence of significant elevation in the osteolysis inductor IL-6 values, reinforce the potential of this superior wear-resistant composite for future orthopedic applications, when compared to traditional UHMWPE.

Experimental study on a method of in vitro preparation and seperation for metallic prosthesis wear particles / 中国矫形外科杂志

[Objective]To design a method of in vitro preparation and seperation for metallic wear particles around joint prosthesis and evaluate its feasibility in medical experiments.[Method]Ti-6Al-4V and Co-Gr-Mo alloys were used to make two friction jars respectirely. National inventive patent applied number 03142073.7.Lots of quadrate blocks made of the same materials are put into the jars respectively,which were then.lubri cated by man-made body fluid and vibrated on a bottle shaker.After 21 days the fluid was harvested and centrifuged to get the produced wear particles.The collected particles were studied by using element trace analysis,laser countersizer and scanning electron microscopy.The J774.A1 macrophages cultured together with these particles for 24 hours were observed under inverted phase contrast microscopy and transmission electron microscopy.[Result]A got great amounts of metallic particles with 1?m diameter coned beproduce using this method.The aver age diameter of titanium alloys(Dv90) is 1.011 and that of Co-Gr-Mo is 1.010.Particle size distribution had good consistency in different materials.Under scanning electron microscopy ,the particles had irregular shapes just like those got from revision operations.The particles taken into the J774.A1 macrophages could be seen under inverted p hase contrast microscopy and transmission electron microscopy.[Conclusion]This method is good enough to producl lots of metallic wear particles mosth like those around total joint prosthesis and can be used in further in vivo and in vitro studies about joint prosthesis loosening.

Preparation of metallic wear particles around joint prosthesis by vacuum ball mill in vitro / 中国矫形外科杂志

[Objective]To investigate a method of in vitro preparation and separation for metallic wear particles around joint prosthesis,and evaluate its feasibility in medical experiments of prosthetic loosening.[Method]Metallic wear particles were made around joint prosthesis by vacuum ball mill in vitro.Particle size,size distribution,chemical composition and shape were characterized by element trace analysis,laser countersizer,scanning electron microscopy.Metal particles were co-cultured with RAW264.7 cells,and its cytotoxicity was detected.[Result]Metal particles made by vacuum ball mill in vitro was similar to particles extracted in vivo(

An Inguinal Mass associated with Polyethylene Wear Debris after a Total Hip Arthroplasty: A Case Report / 대한정형외과학회잡지

Ostelolysis and implant loosening by wear particles after a total hip arthroplasty is a well-documented phenomenon. Howerver, the occurrence of a soft tissue mass around the hip joint after a total hip arthroplasty is rare. We experienced a case of an inguinal mass associated with polyethylene wear particles. An excision of the mass and revision arthroplasty for a polyethylene liner and metal head were performed successfully via a separate incision. We describe this rare case with a review of the relevant literature.

Preventive and Mitigative Effects of Alendronate on Osteolysis induced by Particulate Debris: Quantitative and Comparative Analysis Using Mouse Calvarial Model / 대한정형외과학회잡지

PURPOSE: Wear particle induced osteolysis is a serious complication in total joint arthroplasty. The purpose of this study was to compare the preventive and mitigative effects of alendronate on particle induced osteolysis among particles using mouse calvarial model. MATERIALS AND METHODS: Seventy-two mice were randomized into sham group, Ti6Al4V group, CoCr- Mo group and Ultra High Molecular Weight Polyethylene (UHMWPE) group according to the particles treated to the calvarial tissues. Each group was divided into control subgroup which received no alendronate, preventive subgroup which received alendronate for 4 weeks after particle distribution and therapeutic subgroup which received alendronate for 3 weeks after 1 week delay from particle distribution. We evaluated the effects quantitatively using histomorphometry. Number of osteoclast, fibrous thickness, eroded bone surface area, bone thickness and bone volume were measured and compared. RESULTS: Alendronate showed significant preventive and mitigative effects on osteolysis induced by Ti6Al4V particles and showed significant preventive and somewhat less mitigative effect on osteolysis by CoCrMo particles. On UHMWPE particles, alendronate showed no preventive and mitigative effects. CONCLUSION: Alendronate may be useful in preventing osteolysis induced by metal particles but had no effect on ostelysis induced by UHMWPE particles.