Evidence mapPaperPMID 40993116Full record

ArticleBone research2025

Mechanism of Piezo1 regulating chondrocyte mitochondrial function and promoting fracture healing through β-catenin/LARS2 signaling pathway.

Tao Zhang, Hongzhi Lv, Siming Jia, Lijun Wang, Weijian Liu, Kai Ding, Xiaofeng Du, Guangzhao Hou, Zhiyong Hou, Yingze Zhang and 3 more

Abstract read
In one paragraph

Article in Bone research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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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

6 citing papers in PubMed.

  1. Article
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  6. 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

13 authors.

Tao Zhang *Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China.
Hongzhi Lv *Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China.
Siming Jia *Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China.
Lijun WangHainan Institute of Regenerative Orthopedics and Sports Medicine, Hainan Academy of Medical Sciences and School of Basic Medicine, Hainan Medical University, Haikou, Hainan, China. wanglijun2014@sibcb.ac.cn.
Weijian LiuDepartment of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, China.
Kai DingDepartment of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China.
Xiaofeng DuDepartment of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China.
Guangzhao HouDepartment of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China.
Zhiyong HouDepartment of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China.ORCID http://orcid.org/0000-0001-5838-4025
Yingze ZhangDepartment of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China.
Weiguo ZouHainan Institute of Regenerative Orthopedics and Sports Medicine, Hainan Academy of Medical Sciences and School of Basic Medicine, Hainan Medical University, Haikou, Hainan, China.ORCID http://orcid.org/0000-0003-2516-0302
Wei ChenDepartment of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China. surgeonchenwei@126.com.ORCID http://orcid.org/0000-0001-5451-6430
Yanbin ZhuDepartment of Orthopaedic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, Hebei, China. 38600312@hebmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Piezo1, a key mechanosensor in bone homeostasis, plays a crucial role in fracture healing. However, the mechanisms through which Piezo1 regulates chondrocytes and affects endochondral ossification remain poorly understood. This study aimed to investigate the regulatory mechanisms of Piezo1 in chondrocytes during endochondral ossification. Using lineage tracing, we identified chondrocyte-to-osteoblast transdifferentiation during endochondral ossification, which was impaired by chondrocyte-specific Piezo1 knockout. Piezo1 deficiency disrupted mitochondrial bioenergetics, characterized by diminished membrane potential, reduced adenosine triphosphate (ATP) synthesis, suppressed oxygen consumption rates (basal and maximal respiration), and elevated mitochondrial superoxide generation, thereby impairing endochondral ossification during fracture healing. Single-cell RNA sequencing revealed upregulated Lars2 expression in hypertrophic chondrocytes following Piezo1 knockout. Inhibition of Lars2 in chondrocytes normalized mitochondrial dynamics-related markers (MFN1, MFN2, OPA1, DRP1) and restored mitochondrial functional homeostasis. This intervention concurrently reversed Piezo1 knockout-induced suppression of osteogenic markers (Col1, ALP, OCN, OPN, RUNX2), thereby enhancing fracture repair. Protein interaction analyses confirmed direct binding between β-catenin and Lars2. Mechanistically, Piezo1 governs Lars2 expression via β-catenin signaling. Our findings demonstrate that Piezo1 activation via Yoda1 enhances mitochondrial bioenergetics and accelerates fracture repair through the β-catenin/Lars2 axis, offering novel insights and therapeutic avenues for fracture treatment.

Indexed as

beta CateninChondrocytesFracture HealingIon ChannelsMitochondriaAnimalsMiceMice, Inbred C57BLMice, KnockoutOsteogenesisSignal Transductionbeta CateninIon ChannelsPiezo1 protein, mouse

Identifiers

PMID40993116
PMCPMC12460606

What Socratic holds

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LicenceCC BY
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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 Socratic graph.