Propionate and butyrate attenuate macrophage pyroptosis and osteoclastogenesis induced by CoCrMo alloy particles  

作　　者：Yang-Lin Wu Chen-Hui Zhang Yun Teng Ying Pan Nai-Cheng Liu Pei-Xin Liu Xu Zhu Xin-Lin Su Jun Lin 

机构地区：[1]Department of Orthopaedics,Suzhou Dushu Lake Hospital,Dushu Lake Hospital Affiliated to Soochow University,Medical Centre of Soochow University,Suzhou 215001,Jiangsu,China [2]Department of Orthopaedics,the First Affiliated Hospital of Soochow University,Soochow University,Suzhou 215006,Jiangsu,China [3]Department of Infectious Diseases,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China

出　　处：《Military Medical Research》2023年第2期191-206,共16页军事医学研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(81871789,81802200,82172387);the Natural Science Foundation of Jiangsu Province(BK20180052);the Gusu Health Talents Program(GSWS2020023)。

摘　　要：Background:Wear particles-induced osteolysis is a major long-term complication after total joint arthroplasty.Up to now,there is no effective treatment for wear particles-induced osteolysis except for the revision surgery,which is a heavy psychological and economic burden to patients.A metabolite of gut microbiota,short chain fatty acids(SCFAs),has been reported to be beneficial for many chronic inflammatory diseases.This study aimed to investigate the therapeutic effect of SCFAs on osteolysis.Methods:A model of inflammatory osteolysis was established by applying CoCrMo alloy particles to mouse calvarium.After two weeks of intervention,the anti-inflammatory effects of SCFAs on wear particle-induced osteolysis were evaluated by micro-CT analysis and immunohistochemistry staining.In vitro study,lipopolysaccharide(LPS)primed bone marrow-derived macrophages(BMDMs)and Tohoku hospital pediatrics-1(THP-1)macrophages were stimulated with CoCrMo particles to activate inflammasome in the presence of acetate(C2),propionate(C3),and butyrate(C4).Western blotting,enzyme-linked immunosorbent assay,and immunofluorescence were used to detect the activation of NLRP3 inflammasome.The effects of SCFAs on osteoclasts were evaluate by qRT-PCR,Western blotting,immunofluorescence,and tartrate-resistant acid phosphatase(TRAP)staining.Additionally,histone deacetylase(HDAC)inhibitors,agonists of GPR41,GPR43,and GPR109A were applied to confirm the underlying mechanism of SCFAs on the inflammasome activation of macrophages and osteoclastogenesis.Results:C3 and C4 but not C2 could alleviate wear particles-induced osteolysis with fewer bone erosion pits(P<0.001),higher level of bone volume to tissue volume(BV/TV,P<0.001),bone mineral density(BMD,P<0.001),and a lower total porosity(P<0.001).C3 and C4 prevented CoCrMo alloy particles-induced ASC speck formation and nucleationinduced oligomerization,suppressing the cleavage of caspase-1(P<0.05)and IL-1β(P<0.05)stimulated by CoCrMo alloy particles.C3 and C4 also inhibited the generation of gasder

关 键 词：NLRP3 inflammasome PYROPTOSIS Short chain fatty acids OSTEOLYSIS OSTEOCLAST 

分 类 号：R687.4[医药卫生—骨科学]