Evidence map›Paper›PMID 25403236›Full record

ArticleArthritis research & therapy2014

Local intra-articular injection of rapamycin delays articular cartilage degeneration in a murine model of osteoarthritis.

Koji Takayama, Yohei Kawakami, Makoto Kobayashi, Nick Greco, James H Cummins, Takehiko Matsushita, Ryosuke Kuroda, Masahiro Kurosaka, Freddie H Fu, Johnny Huard

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 1 pooled it
10.7field-weighted citation impact, top 1% of its field
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

104 citing papers in PubMed, 1 synthesis or guideline pooled it, 199 citations in OpenAlex.

  1. Pooled it
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  11. Liposome-Based Interventions in Knee Osteoarthritis.Small (Weinheim an der Bergstrasse, Germany) · 2025
    Review
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  13. Inhibition of mTORC1 by rapamycin results in feedback activation of AktbioRxiv : the preprint server for biology · 2025
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44 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 2 countries.

Koji Takayama
Yohei Kawakami
Makoto Kobayashi
Nick Greco
James H Cummins
Takehiko Matsushita
Ryosuke Kuroda
Masahiro Kurosaka
Freddie H Fu
Johnny Huard
University of Pittsburgh · USKobe University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionRecent studies have revealed that rapamycin activates autophagy in human chondrocytes preventing the development of osteoarthritis (OA) like changes in vitro, while the systemic injection of rapamycin reduces the severity of experimental osteoarthritis in a murine model of OA in vivo. Since the systemic use of rapamycin is associated with numerous side effects, the goal of the current study was to examine the beneficial effect of local intra-articular injection of rapamycin in a murine model of OA and to elucidate the mechanism of action of rapamycin on articular cartilage.

methodsDestabilization of the medial meniscus (DMM) was performed on 10-week-old male mice to induce OA. Intra-articular injections of 10 μl of rapamycin (10 μM) were administered twice weekly for 8 weeks. Articular cartilage damage was analyzed by histology using a semi-quantitative scoring system at 8 and 12 weeks after surgery. Mammalian target of rapamycin (mTOR), light chain 3 (LC3), vascular endothelial growth factor (VEGF), collagen, type X alpha 1 (COL10A1), and matrix metallopeptidase 13 (MMP13) expressions were analyzed by immunohistochemistry. VEGF, COL10A1, and MMP13 expressions were further examined via quantitative RT-PCR (qPCR).

resultsIntra-articular injection of rapamycin significantly reduced the severity of articular cartilage degradation at 8 and 12 weeks after DMM surgery. A reduction in mTOR expression and the activation of LC3 (an autophagy marker) in the chondrocytes was observed in the rapamycin treated mice. Rapamycin treatment also reduced VEGF, COL10A1, and MMP13 expressions at 8 and 12 weeks after DMM surgery.

conclusionThese results demonstrate that the intra-articular injection of rapamycin could reduce mTOR expression, leading to a delay in articular cartilage degradation in our OA murine model. Our observations suggest that local intra-articular injection of rapamycin could represent a potential therapeutic approach to prevent OA.

Indexed as

Disease Models, AnimalAnimalsCartilage, ArticularImmunosuppressive AgentsInjections, Intra-ArticularMaleMiceOsteoarthritisSirolimusImmunosuppressive AgentsSirolimus

Identifiers

PMID25403236
PMCPMC4269094
OpenAlexW2110068403

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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 OpenQuestion graph.