Evidence map›Paper›PMID 42096091›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2026

Melatonin improves osteogenic differentiation in a high-glucose environment by activating NRF2 to promote autophagy through the regulation of cross-talk between macrophages and bone marrow mesenchymal stem cells.

Jimei Zhang, Ling Zhu, Jianping Zhou, Qunying Yu, Guangyuan Yang, Chaoli Luo, Jianguo Meng, Kewang Mao, Jing Liu, Donggang Mou and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Review
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

11 authors.

Jimei Zhang *Gastroenterology Department, Chenggong Hospital, Yan'an Hospital Affiliated to KunmingMedical University, Kunming, 650505, Yunnan, China.
Ling Zhu *Orthopedics Department, Chenggong Hospital, Yan'an Hospital Affiliated to KunmingMedical University,, Kunming, 650505, Yunnan, China.
Jianping ZhouOrthopedics Department, Chenggong Hospital, Yan'an Hospital Affiliated to KunmingMedical University,, Kunming, 650505, Yunnan, China.
Qunying YuObstetrics Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650000, Yunnan, China.
Guangyuan YangKunming Medical University, Kunming, 650500, Yunnan, China.
Chaoli LuoOperating Room, Yunnan Pain Disease Hospital, Kunming, 650000, Yunnan, China.
Jianguo MengOrthopedics Department, Guang Nan Hospital of Traditional Chinese Medicine, Guangnan, 663300, Yunnan Province, China.
Kewang MaoOrthopedics Department, Hua Ning Country Hospital, Huaning, 652800, Yunnan, China.
Jing LiuOrthopedics Department, Chenggong Hospital, Yan'an Hospital Affiliated to KunmingMedical University,, Kunming, 650505, Yunnan, China.
Donggang MouPain Department, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, 650055, Yunnan, China.
Xuming YangOrthopedics Department, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, 650055, Yunnan, China. yangxmkm@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMelatonin (MT) can regulate the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but its effect on the osteogenic differentiation of BMSCs under high glucose (HG) conditions is unclear. Therefore, in this study, the effect of MT on the osteogenic differentiation of BMSCs under HG conditions was investigated.

methodsA mouse model of diabetic osteoporosis (DOP) was induced by the intraperitoneal injection of streptozotocin (STZ), and macrophages or BMSCs were cultured with 25 mM glucose to construct an in vitro cell model. Different doses of MT were used to treat the mice or cells. Genes and proteins were assessed through RT‒qPCR and Western blotting. ALP staining, alizarin red staining, and HE staining were used to assess the osteogenic differentiation of BMSCs and the advancement of DOP in mice.

resultsUnder normal conditions, MT could increase the expression of osteogenic differentiation-related proteins RUNX2, OCN, and OPN, and enhance differentiation and mineralization levels in BMSCs; however, MT failed to stimulate osteogenic differentiation in BMSCs under HG conditions. Furthermore, regardless of whether under HG conditions, in macrophages, MT suppressed the expression of the M1 phenotype markers CD86, iNOS, and CCR7 while increasing the expression of the M2 phenotype markers CD206, Arg1, and Ym1. Subsequent experiments revealed that under HG conditions, MT indirectly promoted the osteogenic differentiation of BMSCs through the enhancement of the M2 polarization of macrophages; however, MT was unable to directly influence the osteogenic differentiation of BMSCs. Additionally, in mouse experiments, administering high doses of MT effectively mitigated DOP by lowering blood glucose levels, ameliorating pathological damage in femoral tissues, and enhancing collagen accumulation and osteogenic markers expression. From a mechanistic standpoint, MT triggered autophagy by counteracting the suppressive effect of HG on NRF2, thus reducing HG-triggered ROS generation and inflammation in macrophage, promoting the M2 polarization of macrophages, and mitigating the suppressive effect of HG on the osteogenic differentiation of BMSCs.

conclusionOur study indicates that under HG conditions, MT improves osteogenic differentiation by regulating the crosstalk between M2 macrophages and BMSCs.

Indexed as

MacrophagesMelatoninMesenchymal Stem CellsNF-E2-Related Factor 2OsteogenesisAnimalsAutophagyCell DifferentiationCells, CulturedDiabetes Mellitus, ExperimentalGlucoseMaleMiceMice, Inbred C57BLOsteoporosisGlucoseMelatoninNfe2l2 protein, mouseNF-E2-Related Factor 2AutophagyBone marrow mesenchymal stem cellsMacrophage M2 polarizationMelatoninNRF2Osteogenic differentiation

Identifiers

PMID42096091

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.