Evidence map›Paper›PMID 34092246›Full record

ArticleJournal of nanobiotechnology2021

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

Yanglin Wu, Fan He, Chenhui Zhang, Qin Zhang, Xinlin Su, Xu Zhu, Ang Liu, Weidong Shi, Weifeng Lin, Zhongqin Jin and 2 more

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  16. CombiningFrontiers in cell and developmental biology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Yanglin Wu *Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Fan He *Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215007, China.
Chenhui ZhangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Qin ZhangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Xinlin SuDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Xu ZhuDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Ang LiuDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Weidong ShiDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Weifeng LinDepartment of Materials and Interfaces, Weizmann Institute of Science, 76100, Rehovot, Israel.
Zhongqin JinDepartment of Digestive, Children's Hospital Affiliated to Soochow University, Suzhou, China. sunyu0628@126.com.
Huilin YangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China. suzhouspine@163.com.
Jun LinDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, No. 188 Shizi Street, Suzhou, 215006, Jiangsu, China. linjun@suda.edu.cn.ORCID http://orcid.org/0000-0002-8094-5826

Funding

Gusu Health Talents Program GSWS2020023National Natural Science Foundation of China 81871789National Natural Science Foundation of China (CN) 31771063National Natural Science Foundation of China (CN) 81802200National Natural Science Foundation of China (CN) 82101033National Natural Science Foundation of China (CN) 82171333Natural Science Foundation of Jiangsu Province (CN) BK20180052
6 · The paper itself

Abstract

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.

Indexed as

AnimalsButyratesFatty Acids, VolatileFecesGastrointestinal MicrobiomeHomeostasisMaleMelatoninMiceMice, Inbred C57BLMice, KnockoutNanoparticlesNLR Family, Pyrin Domain-Containing 3 ProteinOsteolysisReceptors, G-Protein-CoupledRNA, Ribosomal, 16SButyratesFatty Acids, VolatileHcar2 protein, mouseMelatoninNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseReceptors, G-Protein-CoupledRNA, Ribosomal, 16STitaniumButyrateGPR109AGut microbiotaInflammatory osteolysisNLRP3 inflammasome

Identifiers

PMID34092246
PMCPMC8182936

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.