Evidence map›Paper›PMID 39826612›Full record

ArticleJournal of advanced research2025

Transcriptional regulation of Rankl by Txnip-Ecd in aging and diabetic related osteoporosis.

Xiankun Cao, Kexin Liu, Jinbo Yuan, Qi Hua, Kewei Rong, Tangjun Zhou, Wenxin He, Yichuan Pang, Xiao Yang, Yating Yu and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Recent Updates on Diabetes and Bone.International journal of molecular sciences · 2025
    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

17 authors.

Xiankun CaoShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Kexin LiuShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Jinbo YuanSchool of Biomedical Sciences, the University of Western Australia, Perth, Western Australia 6009, Australia.
Qi HuaShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Kewei RongShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Tangjun ZhouShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Wenxin HeShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; Centre National de la Recherche Scientifique-Laboratoire International Associé (CNRS-LIA) Hematology and Cancer, Sino-French Research Center for Life Sciences and Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Yichuan PangDepartment of Nuclear Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200011, China.
Xiao YangShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Yating YuDepartment of Orthopedic and Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Road, Shanghai 200011, People's Republic of China.
Pu ZhangShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Peixiang MaShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Yu CaoDepartment of Orthopedic and Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Road, Shanghai 200011, People's Republic of China.
Jie ZhaoShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: Profzhaojie@126.com.
Grant MorahanHarry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, 6 Verdun Street, Nedlands, Perth, WA 6009, Australia; Australian Centre for Advancing Diabetes Innovations, The University of Melbourne, Parkville, Victoria 3050, Australia. Electronic address: grant.morahan@perkins.org.au.
Jiake XuSchool of Biomedical Sciences, the University of Western Australia, Perth, Western Australia 6009, Australia; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Electronic address: jiake.xu@uwa.edu.au.
An QinShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: dr_qinan@shsmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionBone homeostasis between osteoclast bone resorption and osteoblastic bone formation is tightly regulated by a series of factors such as the receptor activator of nuclear factor-κB ligand (RANKL). Denosumab that neutralizes RANKL is effective and widely applied in the treatment of postmenopausal osteoporosis. However, factors that participated in the RANKL-related bone remodeling process in primary and secondary osteoporosis are less known.

objectivesRevealing the novel transcriptional regulatory mechanism of RANKL is of great significance for the treatment of osteoporosis.

methodsAfter differential expression genes (DEGs) intersection and screening, we generated Thioredoxin-interacting protein (Txnip) bone marrow-derived mesenchymal stromal cells (BMSCs) genetic knockout mice and performed bone histomorphometry and histological analysis. RNA-Sequencing, Western blotting and immunofluorescence staining verified Rankl downregulation. Co-immunoprecipitation and immunofluorescence staining were used for Rankl regulation mechanism exploration. A specific inhibitor was selected for treatment effect verification.

resultsTxnip knockout in BMSCs impaired its osteogenic differentiation, suppressed Rankl expression and subsequent osteoclast formation and thus led to increased bone mass. The regulatory function of Txnip on Rankl expression was revealed for the first time through the novel transcription-related Ecdysoneless (Ecd)-P300 axis. Pharmacological inhibition of Txnip can effectively prevent bilateral ovariectomy (OVX)-induced osteoporosis.

conclusionsInhibition of Txnip is an alternative way to suppress Rankl-mediated osteoblast and osteoclast crosstalk. This interesting finding rendered Txnip an ideal therapeutic target for the treatment of both ovariectomy-induced and diabetes-induced osteoporosis.

Indexed as

AgingCarrier ProteinsOsteoporosisRANK LigandThioredoxinsAnimalsCell DifferentiationFemaleGene Expression RegulationHumansMesenchymal Stem CellsMiceMice, Inbred C57BLMice, KnockoutOsteoclastsOsteogenesisCarrier ProteinsRANK LigandThioredoxinsTnfsf11 protein, mouseTxnip protein, mouseBone remodelingOsteoblastOsteoporosisReceptor activator of nuclear factor-κB ligand (Rankl)Thioredoxin-interacting protein (Txnip)

Identifiers

PMID39826612
PMCPMC12627875

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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.