Evidence map›Paper›PMID 41217833›Full record

ArticleJCI insight2026

GDF15 induces excessive activation of osteoclasts within the vertebral endplates leading to early endplate degeneration.

Xiaoqun Li, Jinhui Wu, Qingjie Kong, Miao Hu, Yuhong Li, Ziheng Wei, Heng Jiang, Xuhui Zhou, Jun Ma

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

9 authors.

Xiaoqun LiDepartment of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China.
Jinhui WuDepartment of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Qingjie KongDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Miao HuDepartment of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Yuhong LiDepartment of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China.
Ziheng WeiDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Heng JiangDepartment of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Xuhui ZhouDepartment of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Jun MaDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Modic type 1 and 2 changes (MC-1 and MC-2) are highly prevalent in individuals with chronic low back pain, yet the cellular and molecular mechanisms underlying vertebral endplate degeneration remain poorly defined. Here, we report that osteoclastogenesis is markedly elevated in MC-1 and MC-2 lesions compared with MC-3 lesions, suggesting an active role for osteoclasts in the early stages of degeneration. Using a lumbar spine instability (LSI) mouse model, we demonstrate enhanced osteoclast activity in degenerating endplates. RNA sequencing of mononuclear cells isolated from the endplate and adjacent subchondral bone identified Gdf15 as a potential upstream regulator of this process. Conditional knockout of Gdf15 in monocytes reduced osteoclast formation, aberrant CD31hiEmcnhi angiogenesis, and pain-associated neurogenesis, ultimately mitigating endplate degeneration and mechanical allodynia. Mechanistically, GDF15 promoted the fusion of preosteoclasts by modulating the expression of Rho family small GTPases. In a humanized GDF15 knockin mouse model, therapeutic neutralization of GDF15 led to a reduction in osteoclast burden, improved endplate structure, and attenuated pain behavior. Together, these findings uncover a previously unrecognized role for GDF15 in driving osteoclast-mediated endplate degeneration and highlight its potential as a therapeutic target for the treatment of endplate-related chronic low back pain.

Indexed as

Growth Differentiation Factor 15Intervertebral Disc DegenerationLow Back PainLumbar VertebraeOsteoclastsAnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, KnockoutOsteogenesisGdf15 protein, mouseGrowth Differentiation Factor 15AgingBone biologyMouse modelsOsteoclast/osteoblast biology

Identifiers

PMID41217833
PMCPMC12890488

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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.