Evidence map›Paper›PMID 36066338›Full record

ArticleBone & joint research2022

Exosomes from dysfunctional chondrocytes affect osteoarthritis in Sprague-Dawley rats through FTO-dependent regulation of PIK3R5 mRNA stability.

Guohua Lv, Bing Wang, Lei Li, Yunchao Li, Xinyi Li, Haoyu He, Lei Kuang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bone & joint research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

20 citing papers in PubMed, 29 citations in OpenAlex.

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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

7 authors at 1 institution in 1 country.

Guohua LvDepartment of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Bing WangDepartment of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Lei LiDepartment of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Yunchao LiDepartment of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Xinyi LiDepartment of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Haoyu HeDepartment of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Lei KuangDepartment of Spine Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.ORCID 0000-0003-0285-4117
Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsExosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages.

methodsRat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot.

resultsDC-exo inhibited macrophage autophagy (p = 0.002) and promoted M1 macrophage polarization (p = 0.002). DC-exo at 20 μg/ml induced collagen degradation (p < 0.001) and inflammatory cell infiltration (p = 0.023) in rats. OANCT was elevated in DC (p < 0.001) and in cartilage tissues of OA patients (p < 0.001), and positively correlated with patients' Kellgren-Lawrence grade (p < 0.001). PIK3R5 was increased in DC-exo-treated cartilage tissues (p < 0.001), and OANCT bound to fat mass and obesity-associated protein (FTO) (p < 0.001). FTO bound to PIK3R5 (p < 0.001) to inhibit the stability of PIK3R5 messenger RNA (mRNA) (p < 0.001) and disrupt the PI3K/AKT/mTOR pathway (p < 0.001).

conclusionExosomal OANCT from DC could bind to FTO protein, thereby maintaining the mRNA stability of PIK3R5, further activating the PI3K/AKT/mTOR pathway to exacerbate OA.Cite this article:

Indexed as

autophagycartilage tissueschondrocytesDysfunctional chondrocyte-derived exosomesFTOLong non-coding RNA OANCTmacrophagesmRNAsOsteoarthritisOsteoarthritis (OA)PIK3R5rat modellingRNAsSprague-Dawley ratswestern blot

Identifiers

PMID36066338
PMCPMC9533253
OpenAlexW4294755200

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.