Evidence map›Paper›PMID 41813908›Full record

ArticleExperimental & molecular medicine2026

Osteoblast-derived osteomodulin restrains osteoclastogenesis via ITGB8/RRM2-mediated reduction of mitochondrial respiration and mitochondrial ATP production.

Xiaowen Jiang, Han Chen, Weiduo Hou, Chengxin Dai, Ruijie Zhang, Erman Chen, Jingjing Zhang, Wanyi Wu, Jianbin Xu, Mo Chen and 9 more

Abstract read
In one paragraph

Article in Experimental & molecular medicine, 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. Article
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

19 authors.

Xiaowen Jiang *Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Han Chen *Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Weiduo HouDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Chengxin DaiTaizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Wenzhou, China.
Ruijie ZhangDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Erman ChenDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Jingjing ZhangCollege of Pharmacy, Hangzhou Normal University, Hangzhou, China.
Wanyi WuCollege of Pharmacy, Hangzhou Normal University, Hangzhou, China.
Jianbin XuDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Mo ChenDepartment of Rheumatology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Liang LiuDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Xun TanDepartment of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Xiaoxiao JiDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Xiaoyong WuDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Kanbin WangDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Chaorong YuDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Xiaohua YuDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Xiaohua.yu@zju.edu.cn.
Weixu LiDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. zrlwx@zju.edu.cn.
Wei ZhangDepartment of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. zhangweilook@zju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteoporosis is driven in part by excessive osteoclast-mediated bone resorption, yet osteoblast-derived extracellular cues that restrain osteoclast bioenergetics remain incompletely defined. Here we identify osteomodulin (OMD), a matrix-associated osteoblast-derived protein that is reduced in the bone tissue and serum of postmenopausal patients with osteoporosis. Inducible global or osteoblast-specific Omd deletion exacerbates bone loss and increases osteoclast activity, whereas osteoclast precursor-specific deletion produces no overt skeletal phenotype. Mechanistically, OMD engages integrin β8 on osteoclast precursors, suppresses RhoA activity and enhances YAP phosphorylation, thereby reducing YAP/TEAD occupancy at the ribonucleotide reductase M2 (RRM2) promoter and repressing Rrm2 transcription. Consistent with RRM2's role in maintaining the dNTP pools required for mitochondrial DNA replication, OMD decreases mtDNA copy number and the abundance of electron transport chain proteins, leading to reduced mitochondrial respiration and ATP production, with only limited glycolytic compensation. Finally, recombinant OMD supplementation or pharmacologic RRM2 inhibition mitigates ovariectomy and lipopolysaccharide-induced bone loss. Together, our findings identify an OMD-integrin β8-RhoA-YAP/TEAD-RRM2 axis that links extracellular matrix signaling to mitochondrial respiration and mitochondrial ATP production during osteoclastogenesis.

Indexed as

Adenosine TriphosphateExtracellular Matrix ProteinsMitochondriaOsteoblastsOsteogenesisAnimalsCell RespirationFemaleHumansMiceMice, KnockoutOsteoclastsAdenosine TriphosphateExtracellular Matrix Proteins

Identifiers

PMID41813908
PMCPMC13049008

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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.