Evidence map›Paper›PMID 40461512›Full record

ArticleBone research2025

AIDS patients suffer higher risk of advanced knee osteoarthritis progression due to lopinavir-induced Zmpste24 inhibition.

Keyu Kong, Li Liu, Renfang Zhang, Yongyun Chang, Yueming Shao, Chen Zhao, Hua Qiao, Minghao Jin, Xuzhuo Chen, Wentao Shi and 11 more

Abstract read
PubMed Full text at PMC Publisher
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 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

21 authors.

Keyu Kong *Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Li Liu *Department of Infection and Immunity, Shanghai Public Health Clinical Center (SPHCC), Fudan University, Shanghai, China.
Renfang Zhang *Department of Infection and Immunity, Shanghai Public Health Clinical Center (SPHCC), Fudan University, Shanghai, China.
Yongyun ChangShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Yueming ShaoDepartment of Infection and Immunity, Shanghai Public Health Clinical Center (SPHCC), Fudan University, Shanghai, China.
Chen ZhaoShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Hua QiaoShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Minghao JinShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xuzhuo ChenShanghai Key Laboratory of Stomatology, Department of Oral Surgery, College of Stomatology, Ninth People's Hospital, Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wentao ShiDepartment of Biostatistics in Clinical Research Unit, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xinru WuShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Wenxuan FanShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Yuehao HuShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Kewei RongShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Pu ZhangShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Baixing LiShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Jingwei ZhangShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Peixiang MaShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xiaoling ZhangDepartment of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. xlzhang@shsmu.edu.cn.ORCID http://orcid.org/0000-0002-0134-1347
Huiwu LiShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. huiwu1223@163.com.ORCID http://orcid.org/0000-0002-2084-2737
Zanjing ZhaiShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. zanjing_zhai@163.com.ORCID http://orcid.org/0000-0002-0312-7539

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82472476Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality) 23ZR1437300
6 · The paper itself

Abstract

Debate regarding the premature aging of knee joints in acquired immune deficiency syndrome (AIDS) patients has remained contentious, with conjectures pointing towards its correlation with distinct antiviral regimes. Protease inhibitors (PIs) stand as a prominent class of antiviral agents frequently utilized in AIDS management and have been significantly linked to premature senescence. This study aimed to investigate whether PI-containing regimens would accelerate osteoarthritis (OA) development and explore the molecular mechanisms underlying this association. A retrospective cohort of 151 HIV-infected individuals, categorized into PI and non-PI groups, was established. Patients in PI group exhibited lower KOOS and a higher prevalence of radiological knee OA than those in non-PI group. Additionally, 25 anti-HIV drugs were screened and among all antiviral drugs, lopinavir had the most detrimental impact on cartilage anabolism, accelerating cartilage senescence and promoting mouse OA development. Mechanistically, lopinavir accelerated cellular senescence by inhibiting Zmpste24 and interfering nuclear membrane stability, which leads to decreased binding between nuclear membrane-binding protein Usp7 and Mdm2 and activates Usp7/Mdm2/p53 pathway. Zmpste24 overexpression reduces OA severity in mice. These findings suggest that PI-containing regimens accelerate cartilage senescence and OA development through Zmpste24 inhibition, which provides new insights into the selection of HIV regimens.

Indexed as

Acquired Immunodeficiency SyndromeDisease ProgressionLopinavirMembrane ProteinsMetalloendopeptidasesOsteoarthritis, KneeAdultAnimalsCellular SenescenceFemaleHIV Protease InhibitorsHumansMaleMiceMice, Inbred C57BLMiddle AgedHIV Protease InhibitorsLopinavirMembrane ProteinsMetalloendopeptidases

Identifiers

PMID40461512
PMCPMC12134061

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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.