Evidence map›Paper›PMID 39589893›Full record

ArticleJCI insight2024

Mast cell activation by NGF drives the formation of trauma-induced heterotopic ossification.

Tao Jiang, Xiang Ao, Xin Xiang, Jie Zhang, Jieyi Cai, Jiaming Fu, Wensheng Zhang, Zhenyu Zheng, Jun Chu, Minjun Huang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 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

12 authors.

Tao JiangDivision of Spine Surgery, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Academy of Orthopedics, Guangdong Province, Guangzhou, China.
Xiang AoDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Xin XiangDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jie ZhangDivision of Spine Surgery, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Academy of Orthopedics, Guangdong Province, Guangzhou, China.
Jieyi CaiDepartment of General Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Jiaming FuDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Wensheng ZhangDivision of Spine Surgery, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Academy of Orthopedics, Guangdong Province, Guangzhou, China.
Zhenyu ZhengDivision of Spine Surgery, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Academy of Orthopedics, Guangdong Province, Guangzhou, China.
Jun ChuDivision of Spine Surgery, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Academy of Orthopedics, Guangdong Province, Guangzhou, China.
Minjun HuangDivision of Spine Surgery, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Academy of Orthopedics, Guangdong Province, Guangzhou, China.
Zhongmin ZhangDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Liang WangDivision of Spine Surgery, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Academy of Orthopedics, Guangdong Province, Guangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Soft tissue trauma can cause immune system disturbance and neuropathological invasion, resulting in heterotopic ossification (HO) due to aberrant chondrogenic differentiation of mesenchymal stem cells (MSCs). However, the molecular mechanisms behind the interaction between the immune and nervous systems in promoting HO pathogenesis are unclear. In this study, we found that mast cell-specific deletion attenuated localized tissue inflammation, with marked inhibition of HO endochondral osteogenesis. Likewise, blockage of nerve growth factor (NGF) receptor, known as tropomyosin receptor kinase A (TrkA), led to similar attenuations in tissue inflammation and HO. Moreover, while NGF/TrkA signaling did not directly affect MSCs chondrogenic differentiation, it modulated mast cell activation in traumatic soft tissue. Mechanistically, lipid A in LPS binding to TrkA enhanced NGF-induced TrkA phosphorylation, synergistically stimulating mast cells to release neurotrophin-3 (NT3), thereby promoting MSC chondrogenic differentiation in situ. Finally, analysis of single-cell datasets and human pathological specimens confirmed the important role of mast cell-mediated neuroinflammation in HO pathogenesis. In conclusion, NGF regulates mast cells in soft tissue trauma and drives HO progression via paracrine NT3. Targeted early inhibition of mast cells holds substantial promise for treating traumatic HO.

Indexed as

Mast CellsMesenchymal Stem CellsNerve Growth FactorOssification, HeterotopicReceptor, trkAAnimalsCell DifferentiationChondrogenesisDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLMice, KnockoutNeurotrophin 3OsteogenesisNerve Growth FactorNeurotrophin 3Receptor, trkABone biologyBone diseaseImmunologyMast cells

Identifiers

PMID39589893
PMCPMC11721298

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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.