Evidence map›Paper›PMID 41372218›Full record

ArticleNature communications2025

Pla2g7 regulates bone homeostasis via Alox12/12-HETE/Gpr31 signaling axis.

Jiayan Jin, Zeyu Zheng, Jiaxuan Gu, Qibin Zhang, Zhikun Xu, Zhenhua Feng, Siyue Tao, Shumin He, Jiao Cheng, Jian Wang and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. 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

14 authors.

Jiayan Jin *Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zeyu Zheng *Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jiaxuan Gu *School of Life Sciences, Westlake University, Hangzhou, China.
Qibin ZhangDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zhikun XuDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Zhenhua FengDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Siyue TaoDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Shumin HeDepartment of Endocrinology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jiao ChengDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jian WangDepartment of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Hou-Feng ZhengSchool of Life Sciences, Westlake University, Hangzhou, China. houf.zheng@suda.edu.cn.ORCID http://orcid.org/0000-0001-5681-8598
Shishi LiReproductive Medicine Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. lishishi@zju.edu.cn.ORCID http://orcid.org/0000-0002-4763-0419
Fengdong ZhaoDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. zhaofengdong@zju.edu.cn.ORCID http://orcid.org/0000-0002-2945-8707
Jian ChenDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. chenjian-bio@zju.edu.cn.ORCID http://orcid.org/0000-0001-8568-9991

Funding

National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund) 82272520National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund) 82472472
6 · The paper itself

Abstract

Bone homeostasis mainly depends on the equilibrium of osteoclasts and osteoblasts, overactivated osteoclasts play a pivotal role in the progression of osteoporosis. Here, we revealed that Pla2g7 (phospholipase A2 group VII) was positively correlated with bone resorption in clinic. By single-cell RNA-seq data analysis, Pla2g7 was found highly enriched in osteoclasts along the developmental trajectory, which promoted osteoclast differentiation. Inhibition of Pla2g7 by Darapladib impaired both human and mice osteoclast differentiation, meanwhile, Pla2g7-deficient mice showed higher bone mass and restored the ovariectomy-induced bone loss. Mechanistically, we identified that Alox12 (arachidonate 12-lipoxygenase) mediated-arachidonic acid metabolism is a key determinant in Pla2g7 enhanced osteoclast differentiation. Its metabolite 12-HETE (12-hydroxyeicosatetraenoic acid) activated Gpr31 to regulate osteoclast formation via p38 MAPK pathway and mitochondrial energy metabolism. Collectively, our study uncovers an Alox12/12-HETE/Gpr31 axis that regulates Pla2g7-induced osteoclast differentiation, and provides a new insight for osteoporosis treatment.

Indexed as

12-Hydroxy-5,8,10,14-eicosatetraenoic AcidArachidonate 12-LipoxygenaseBone and BonesReceptors, G-Protein-CoupledAnimalsBone ResorptionCell DifferentiationFemaleHomeostasisHumansMiceMice, Inbred C57BLMice, KnockoutOsteoclastsOsteoporosisOvariectomy12-Hydroxy-5,8,10,14-eicosatetraenoic AcidALOX12 protein, humanArachidonate 12-LipoxygenaseReceptors, G-Protein-Coupled

Identifiers

PMID41372218
PMCPMC12748786

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.