ArticleJournal of translational medicine2025
Integrin-mediated SPP1 signaling from macrophages orchestrates extracellular matrix remodeling and chondrogenesis in heterotopic ossification.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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.
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.
Who cites it
6 citing papers in PubMed.
- Biodegradable molybdenum intramedullary nails facilitate fracture repair through neutrophil-mediated immune response.Materials today. Bio · 2026Article
- Persistent ZnAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-Cell dissection of fibrodysplasia ossificans progressiva identifies SPP1 as a mediator of macrophage-fibroadipogenic progenitors crosstalk.Cellular and molecular life sciences : CMLS · 2026Article
- POSTN(+) fibroblasts and SPP1(+) macrophages in scar formation: A review of mechanisms and therapeutic targets (Review).Molecular medicine reports · 2026Review
- Single-cell transcriptome profiling reveals the heterogeneity of ossification of the posterior longitudinal ligament (OPLL) and its immune microenvironment.Cell biology and toxicology · 2026Article
- Baclofen Promotes Osteochondrogenic Commitment of Mesenchymal Stem Cells: Implications for Heterotopic Ossification Risk.International journal of molecular sciences · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
backgroundDifferentiation of mesenchymal progenitor cells (MPCs) is critical pre-requisition for the progression of heterotopic ossification (HO). However, the factors that initiate MPC differentiation remain elusive. This study aims to investigate the temporal crosstalk between macrophages and MPCs during HO, and identified the critical regulatory mechanism.
methodsSingle-cell transcriptome data of mouse ossified hindlimb Achilles’ tendon was acquired from the Gene Expression Omnibus (GEO). MPC and macrophage clusters were visualized, followed by pseudo-time analysis, gene set variation analysis, transcription factor activity analysis, and cell communication analysis. Achilles’ tendon transection and dorsal burn injury was used to induce HO to validate the bioinformatic results. Macrophage-specific delete of Spp1 mouse model was established to observe the effects of macrophage-derived SPP1 on extracellular matrix remodeling and chondrogenesis of MPCs. Pharmacological blocking SPP1-Integrin receptors axis was performed both in vitro and in vivo to identify the essential role of SPP1.
resultsSingle-cell transcriptome profiling analysis revealed Col12a1+ MPCs and SPP1+ macrophages were the critical clusters to initiate and maintain HO. Mechanistically, integrin receptors, especially Itgαv and Itgβ5, were the essential mediator to associate SPP1+ macrophage with MPCs to drive chondrogenesis. In vitro experiments revealed that Spp1 was involved in extracellular matrix (ECM) remodeling and chondrocyte differentiation of mesenchymal progenitor cells. Single cell RNA sequencing combined with in vivo experiments further confirmed that knocking out Spp1 in macrophages significantly alleviated cartilage formation within mouse Achilles’s tendon tissues and HO progression. Specific inhibiting SPP1-Itgαvβ5 axis or knocking out Spp1 gene in macrophages alleviated the progression of HO.
conclusionsOur findings revealed a novel crosstalk between MPC and macrophages via SPP1-integrin receptors axis to promote ECM remodeling and chondrogenic differentiation of MPCs during HO, which may be a potential target for a medical intervention to treat HO.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.