Yanglin Wu1, Fan He2, Chenhui Zhang1, Qin Zhang1, Xinlin Su1, Xu Zhu1, Ang Liu1, Weidong Shi1, Weifeng Lin3, Zhongqin Jin4, Huilin Yang5, Jun Lin6. 1. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China. 2. Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215007, China. 3. Department of Materials and Interfaces, Weizmann Institute of Science, 76100, Rehovot, Israel. 4. Department of Digestive, Children's Hospital Affiliated to Soochow University, Suzhou, China. sunyu0628@126.com. 5. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China. suzhouspine@163.com. 6. Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China. linjun@suda.edu.cn.
Abstract
BACKGROUND: Inflammatory 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. RESULTS: Here, 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. CONCLUSIONS: Taken together, our results suggested that the benefits of melatonin mainly depend on the ability of modulating gut microbiota and regulating butyrate production.
BACKGROUND:Inflammatory 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. RESULTS: Here, 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. CONCLUSIONS: Taken together, our results suggested that the benefits of melatonin mainly depend on the ability of modulating gut microbiota and regulating butyrate production.
Entities:
Keywords:
Butyrate; GPR109A; Gut microbiota; Inflammatory osteolysis; NLRP3 inflammasome
Authors: Lyndsey Burton; Daniel Paget; Nikolaus B Binder; Krista Bohnert; Bryan J Nestor; Thomas P Sculco; Laura Santambrogio; F Patrick Ross; Steven R Goldring; P Edward Purdue Journal: J Orthop Res Date: 2012-08-29 Impact factor: 3.494
Authors: Yang-Lin Wu; Chen-Hui Zhang; Yun Teng; Ying Pan; Nai-Cheng Liu; Pei-Xin Liu; Xu Zhu; Xin-Lin Su; Jun Lin Journal: Mil Med Res Date: 2022-08-23