Melatonin alleviates titanium nanoparticles induced osteolysis via activation of butyrate/GPR109A signaling pathway

Journal of Nanobiotechnology

Zhongqin Jin¹  Weifeng Lin²  Xinlin Su³  Weidong Shi³  Qin Zhang³  Jun Lin³  Chenhui Zhang³  Ang Liu³  Huilin Yang³  Yanglin Wu³  Xu Zhu³  Fan He⁴ 

[1] Department of Digestive, Children’s Hospital Affiliated to Soochow University, Suzhou, China;Department of Materials and Interfaces, Weizmann Institute of Science, 76100, Rehovot, Israel;Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, 215006, Suzhou, Jiangsu, China;Orthopaedic Institute, Medical College, Soochow University, 215007, Suzhou, China;

关键词: Gut microbiota;    Inflammatory osteolysis;    NLRP3 inflammasome;    Butyrate;    GPR109A;   

DOI  :  10.1186/s12951-021-00915-3

来源: Springer

【 摘 要 】

BackgroundInflammatory osteolysis after total joint replacement (TJR) may cause implant failure, periprosthetic fractures, and be a severe threat to global public health. Our previous studies demonstrated that melatonin had a therapeutic effect on wear-particles induced osteolysis. Gut microbiota is closely related to bone homeostasis, and has been proven to be affected by melatonin. However, whether melatonin could play its anti-osteolysis effects through reprogramming gut microbiota remains elusive.ResultsHere, we demonstrated that melatonin could alleviate Ti-particles induced osteolysis, while this therapeutic effect was blocked by antibiotic cocktail treatment. Interestingly, transplantation of fecal microbiota from mice treated with melatonin reappeared the same beneficial effect. Analysis of the 16S rRNA revealed that melatonin could reverse dysbacteriosis triggered by osteolysis, and elevate the relative abundance of some short chain fatty acid (SCFA) producing bacteria. Moreover, butyrate was enriched by exogenous melatonin administration, while acetate and propionate did not show an evident difference. This was consistent with the results of the metagenomic approach (PICRUSt2) analysis, which revealed a general increase in the synthetic enzymes of butyrate. More importantly, direct supplementation of butyrate could also recapitulate the anti-osteolysis effect of melatonin. Further analysis identified that butyrate alleviated osteolysis via activating its receptor GPR109A, and thus to suppress the activation of NLRP3 inflammasome triggered by Ti-particles.ConclusionsTaken together, our results suggested that the benefits of melatonin mainly depend on the ability of modulating gut microbiota and regulating butyrate production.Graphic Abstract

【 授权许可】

CC BY