Evidence mapPaperPMID 41006212Full record

ArticleNature communications2025

Circular RNA-based protein replacement therapy mitigates osteoarthritis in male mice.

Jinlong Suo, Ling Li, Wuyuan Tan, Xubin Yin, Jinghui Wang, Rui Shao, Shaokun Sun, Si-Kun Guo, Jingyi Feng, Bao-Qing Gao and 11 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 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. 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

21 authors.

Jinlong Suo *Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 200233, China. suojinlong2015@sibcb.ac.cn.ORCID http://orcid.org/0000-0003-3389-3776
Ling Li *School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Wuyuan Tan *Department of Plastic and Aesthetic Surgery, Xiangya Hospital, Central South University, Changsha, China.
Xubin YinKey Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Jinghui WangKey Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Rui ShaoInstitute of Microsurgery on Extremities, and Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 200233, China.
Shaokun SunKey Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Si-Kun GuoKey Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Jingyi FengKey Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Bao-Qing GaoCAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Ying WangKey Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Meng-Yuan WeiKey Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Lijun WangHainan Institute of Regenerative Orthopedics and Sports Medicine, Hainan Academy of Medical Sciences, Hainan Medical University, Hainan, China.ORCID http://orcid.org/0000-0002-3686-6098
Heng FengKey Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Xiang GaoKey Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
Ping HuGuangzhou Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong, China.
Xianyou ZhengInstitute of Microsurgery on Extremities, and Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 200233, China.
Ling-Ling ChenSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0000-0001-9501-0305
Guanghua LeiKey Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University, Changsha, China. lei_guanghua@csu.edu.cn.ORCID http://orcid.org/0000-0003-2987-138X
Youkui HuangKey Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. huangyoukui@sibcb.ac.cn.ORCID http://orcid.org/0000-0002-1233-7757
Weiguo ZouInstitute of Microsurgery on Extremities, and Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 200233, China. zouwg94@sibcb.ac.cn.ORCID http://orcid.org/0000-0003-2516-0302

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In vitro-transcribed and circularized RNAs (ivcRNAs) represent a robust platform for sustained protein translation, offering promising potential for localized therapeutic delivery in joint diseases. Osteoarthritis (OA), the most prevalent degenerative joint disorder, remains a major clinical challenge due to its progressive nature and the lack of disease-modifying treatments. In this study, we identify Musashi2 (Msi2) deficiency in articular chondrocytes as a key contributor to OA pathogenesis. To evaluate the efficacy of ivcRNA-mediated protein replacement therapy, we developed a localized delivery strategy that enables high-yield and prolonged protein expression in chondrocytes. Using a destabilization of the medial meniscus (DMM) mouse model, we demonstrate that intra-articular delivery of ivcRNA encoding MSI2 effectively mitigates OA progression in male mice. Furthermore, therapeutic supplementation of SOX5, a downstream effector of MSI2, via ivcRNA delivery further validates this approach. Our findings establish ivcRNA-based protein replacement as a potential RNA therapeutic strategy for osteoarthritis.

Indexed as

OsteoarthritisRNA, CircularAnimalsCartilage, ArticularChondrocytesDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLRNA-Binding ProteinsRNA-Binding ProteinsRNA, Circular

Identifiers

PMID41006212
PMCPMC12474924

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.