Evidence map›Paper›PMID 40426248›Full record

ArticleJournal of orthopaedic surgery and research2025

M2 macrophages activate the IL-10/JAK2/STAT3 pathway to induce pathological microangiogenesis in the nucleus pulposus exacerbating intervertebral disc degeneration.

Si-Ping Zhang, Min Tong, Jun Mo, Zhen-Yu Dong, Yi-Fei Huang

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Article in Journal of orthopaedic surgery and research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

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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

8 citing papers in PubMed.

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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

5 authors.

Si-Ping ZhangThe Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, Xinjiang, 830000, P.R. China.
Min TongThe Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, Xinjiang, 830000, P.R. China.
Jun MoThe Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, Xinjiang, 830000, P.R. China.
Zhen-Yu DongThe Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, Xinjiang, 830000, P.R. China.
Yi-Fei HuangThe Fourth Clinical Medical College of Xinjiang Medical University, Urumqi, Xinjiang, 830000, P.R. China. jerkhuang@163.com.

Funding

Science and Technology Innovation Leading Talents Program - high-level leading talents 2022TSYCLJ0027Xinjiang Uygur Autonomous Region Key Research and Development Program 2022B03011-1
6 · The paper itself

Abstract

backgroundMacrophage infiltration accompanied by pathological microangiogenesis in the nucleus pulposus (NP) plays a critical role in the progression of intervertebral disc degeneration (IDD). However, the involvement of M2 macrophages in mediating NP pathological angiogenesis and their underlying mechanisms remain unclear.

methodsFirstly, the expression of M2 macrophage (CD206) and microangiogenic (CD34) markers in human degenerated NP was observed by immunohistochemical staining, subsequently, a co-culture system of M2 macrophages and NP cells was established. IL-10 expression was silenced using siRNA to assess the pro-angiogenic effects of M2 macrophages in IDD via IL-10 and its downstream janus kinase (JAK) 2/ signal transducer and activator of transcription (STAT) 3 pathway. AG490, a specific JAK2/STAT3 inhibitor, was applied to determine whether IL-10 exerts its effects through this pathway and to evaluate its impact on angiogenesis and extracellular matrix (ECM) metabolism in NP pathology.

resultsCD206 and CD34 were co-expressed in degenerated NP tissue. Degenerated NP cells secreted CCL17, CCL18, and CD206, exhibiting M2-like characteristics. Co-culture of M2 macrophages with degenerated NP cells led to IL-10 secretion to promote CD34 expression, and downregulated anabolic genes (type II collagen (COL2), aggrecan), and upregulated catabolic genes (matrix metalloproteinase (MMP)-3, MMP-7). JAK2 and STAT3 expression was significantly increased following co-culture. Activation of the JAK2/STAT3 pathway enhanced vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), and CD34 expression and induced further downregulation of COL2 and aggrecan and upregulation of MMP-3 and MMP-7.

conclusionM2 macrophage infiltration and pathological neovascularization are prominent in degenerated NP tissue. IL-10 secreted by M2 macrophages activates the JAK2/STAT3 pathway to promote pathological microangiogenesis by up-regulate the expression of VEGF/VEGFR. This process disrupts ECM and accelerates the progression of IDD. CLINICAL TRIAL NUMBER: Not applicable.

Indexed as

Interleukin-10Intervertebral Disc DegenerationJanus Kinase 2MacrophagesNeovascularization, PathologicNucleus PulposusSignal TransductionSTAT3 Transcription FactorAdultAgedCells, CulturedCoculture TechniquesFemaleHumansMaleMiddle AgedIL10 protein, humanInterleukin-10JAK2 protein, humanJanus Kinase 2STAT3 protein, humanSTAT3 Transcription FactorIntervertebral disc degenerationMacrophageMicroangiogenesisNucleus pulposus

Identifiers

PMID40426248
PMCPMC12117970

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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.