Evidence map›Paper›PMID 40148953›Full record

ArticleJournal of translational medicine2025

Circ-ITCH promotes the ubiquitination degradation of HOXC10 to facilitate osteogenic differentiation in disuse osteoporosis through stabilizing BRCA1 mRNA via IGF2BP2-mediated m

Da Zhong, Xi Li, Zhen Yin, Peng Chen, Yusheng Li, Jian Tian, Long Wang, Hua Liu, Ke Yin, Lemei Zhu and 5 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 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

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

6 citing papers in PubMed.

  1. Review
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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

15 authors.

Da ZhongDepartment of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China.
Xi LiDepartment of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China.
Zhen YinDepartment of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China.
Peng ChenDepartment of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China.
Yusheng LiDepartment of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China.
Jian TianDepartment of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China.
Long WangDepartment of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China.
Hua LiuDepartment of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China.
Ke YinThe First Affiliated Hospital, Department of Orthopedics, Hengyang Medical School, University of South China, Hengyang, China.
Lemei ZhuSchool of Public Health, Changsha Medical University, Changsha, China.
Lingyu KongDepartment of Radiology, Xiangya Hospital, Central South University, Changsha, China.
Kunli ChenDepartment of Rehabilitation Medicine, Xiangya Hospital, Central South University, Changsha, China.
Yaochun LiDepartment of Rehabilitation Medicine, Xiangya Hospital, Central South University, Changsha, China.
Chungu HongDepartment of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, China.
Chenggong WangDepartment of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China. wangchenggong@csu.edu.cn.

Funding

Horizontal Research Funding of Central South University JXDY-ZD-20231101National Natural Science Foundation of China 82472609Natural Science Foundation of Hunan Province 2023JJ30941the Fundamental Research Funds for the Central Universities of Central South University the Fundamental Research Funds for the Central Universities of Central South University
6 · The paper itself

Abstract

backgroundOsteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) facilitated by mechanical loading is a promising therapy for disuse osteoporosis (DOP), however, it is difficult to implement mechanical loading for a majority of patients. Our study aims to identify circ-ITCH-mediated novel approach to facilitate osteogenic differentiation in DOP.

methodsA rat DOP model and human BM-MSCs under microgravity condition were generated as in vivo and in vitro models of DOP, respectively. The bone mineral density (BMD) and bone parameters were examined in rats. The histological changes of bones and mineralization were monitored by H&E, Alcian blue and Alizarin red S staining. Co-IP was employed to examine the ubiquitination of HOXC10 and the interaction between HOXC10 and BRCA1. The direct associations among circ-ITCH, IGFBP2 and BRCA1 mRNA were assessed by RIP, FISH and RNA pull-down assays.

resultsCirc-ITCH was downregulated in rat model of DOP and BM-MSCs under microgravity stimulation. Circ-ITCH overexpression promoted osteogenic differentiation in BM-MSCs under microgravity condition. The altered bone parameters, such as BMD, trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular thickness (Tb.Th), and bone microstructure in DOP rats were rescued by circ-ITCH overexpression. Mechanistically, circ-ITCH enhanced the ubiquitination degradation of HOXC10 through enhancing BRCA1 mRNA stability. Circ-ITCH directly bound to IGF2BP2 protein to stabilize BRCA1 mRNA via m

conclusionCirc-ITCH stabilized BRCA1 mRNA via IGF2BP2-mediated m

Indexed as

BRCA1 ProteinCell DifferentiationHomeodomain ProteinsOsteogenesisOsteoporosisProteolysisRNA-Binding ProteinsRNA StabilityUbiquitinationUbiquitin-Protein LigasesAnimalsBone DensityHumansMaleMesenchymal Stem CellsRatsBRCA1 ProteinHomeodomain ProteinsRNA-Binding ProteinsRNA, MessengerUbiquitin-Protein LigasesBRCA1Circ-ITCHDisuse osteoporosism6A modificationOsteogenic differentiationUbiquitination

Identifiers

PMID40148953
PMCPMC11951756

What Socratic holds

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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 Socratic graph.