Evidence map›Paper›PMID 34185425›Full record

ArticleClinical and translational medicine2021

Inhibition of MAGL activates the Keap1/Nrf2 pathway to attenuate glucocorticoid-induced osteonecrosis of the femoral head.

Ning Yang, Houyi Sun, Yi Xue, Weicheng Zhang, Hongzhi Wang, Huaqiang Tao, Xiaolong Liang, Meng Li, Yaozeng Xu, Liang Chen and 3 more

Open access · goldAbstract read
In one paragraph

Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
11.2field-weighted citation impact, top 1% of its field
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

38 citing papers in PubMed, 80 citations in OpenAlex.

  1. Article
  2. [Mechanisms of RNA-binding protein phase separation in steroid-associated necrosis of the femoral head].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
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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

13 authors at 3 institutions in 1 country.

Ning YangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.ORCID 0000-0001-9382-492X
Houyi SunDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Yi XueDepartment of Orthopaedics, Changshu Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Changshu, China.
Weicheng ZhangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Hongzhi WangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Huaqiang TaoDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Xiaolong LiangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Meng LiDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Yaozeng XuDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Liang ChenDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Liang ZhangDepartment of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Lixin HuangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Dechun GengDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
Soochow University · CNCapital Medical University · CNChangshu No.1 People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glucocorticoids (GCs) are used in treating viral infections, acute spinal cord injury, autoimmune diseases, and shock. Several patients develop GC-induced osteonecrosis of the femoral head (ONFH). However, the pathogenic mechanisms underlying GC-induced ONFH remain poorly understood. GC-directed bone marrow mesenchymal stem cells (BMSCs) fate is an important factor that determines GC-induced ONFH. At high concentrations, GCs induce BMSC apoptosis by promoting oxidative stress. In the present study, we aimed to elucidate the molecular mechanisms that relieve GC-induced oxidative stress in BMSCs, which would be vital for treating ONFH. The endocannabinoid system regulates oxidative stress in multiple organs. Here, we found that monoacylglycerol lipase (MAGL), a key molecule in the endocannabinoid system, was significantly upregulated during GC treatment in osteoblasts both in vitro and in vivo. MAGL expression was positively correlated with expression of the NADPH oxidase family and apoptosis-related proteins. Functional analysis showed that MAGL inhibition markedly reduced oxidative stress and partially rescued BMSC apoptosis. Additionally, in vivo studies indicated that MAGL inhibition effectively attenuated GC-induced ONFH. Pathway analysis showed that MAGL inhibition regulated oxidative stress in BMSCs via the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. The expression of Nrf2, a major regulator of intracellular antioxidants, was upregulated by inhibiting MAGL. Nrf2 activation can mimic the effect of MAGL inhibition and significantly reduce GC-induced oxidative damage in BMSCs. The beneficial effects of MAGL inhibition were attenuated after the blockade of the Keap1/Nrf2 antioxidant signaling pathway. Notably, pharmacological blockade of MAGL conferred femoral head protection in GC-induced ONFH, even after oxidative stress responses were initiated. Therefore, MAGL may represent a novel target for the prevention and treatment of GC-induced ONFH.

Indexed as

ApoptosisAnimalsCell DifferentiationFemur HeadGlucocorticoidsKelch-Like ECH-Associated Protein 1MaleMesenchymal Stem CellsMonoacylglycerol LipasesNF-E2-Related Factor 2OsteoblastsOsteonecrosisRatsRats, Sprague-DawleyGlucocorticoidsKEAP1 protein, ratKelch-Like ECH-Associated Protein 1Monoacylglycerol LipasesNfe2l2 protein, ratNF-E2-Related Factor 2apoptosisglucocorticoidsmonoacylglycerol lipaseosteonecrosis of the femoral headoxidative stress

Identifiers

PMID34185425
PMCPMC8167863
OpenAlexW3172439201

What OpenQuestion holds

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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.