ArticleJCI insight2025
Macrophage-derived Spp1 promotes intramuscular fat in dystrophic muscle.
Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Excess muscle plasma membrane leak disrupts ECM content and shifts macrophage-mediated muscle repair.JCI insight · 2026Article
- Cellular senescence links muscle atrophy and posttraumatic osteoarthritis after ACL injury.Function (Oxford, England) · 2026Article
- Macrophage and fibro-adipogenic progenitor communication in skeletal muscle regeneration: tissue homeostasis and pathogenic remodeling.Journal of leukocyte biology · 2026Review
- Stimulation of EGFR signaling in fibro-adipogenic precursors decreases adipogenesis in Duchenne muscular dystrophy.Skeletal muscle · 2026Article
- GSDME-IL-18 pyroptotic axis prevents myosteatosis by expanding tissue-resident macrophages to promote muscle regeneration.The Journal of clinical investigation · 2026Article
- Macrophage Infiltration, Activation, and Therapeutic Implication in Skeletal Muscle Injury and Repair.International journal of molecular sciences · 2026Review
- Macrophage plasticity and metabolic control in muscle repair and disease.Frontiers in immunology · 2026Review
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.bioRxiv : the preprint server for biology · 2025Article
- Heterogeneous Macrophage Activation in Acute Skeletal Muscle Sterile Injury andInternational journal of molecular sciences · 2025Article
- Stromal cells unifying the pathology of acute and chronic skeletal muscle injury - clue for novel biomaterials.Frontiers in bioengineering and biotechnology · 2025Article
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Authors and funding
20 authors.
Funding
Abstract
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder involving cycles of muscle degeneration and regeneration, leading to accumulation of intramuscular fibrosis and fat. Ablation of Osteopontin/Spp1 in a murine model of DMD (mdx) improves the dystrophic phenotype, but the source of Spp1 and its impact on target cells in dystrophic muscles remain unknown. In dystrophic muscles, macrophages are the predominate infiltrating leukocyte and express high levels of Spp1. We used macrophage-specific ablation combined with single-cell transcriptional profiling to uncover the impact of macrophage-derived Spp1 on cell-cell interactions in mdx muscles. Ablation of macrophage-specific Spp1 (cKO) correlated with reduction of 2 PDGFRa+ stromal cell populations, expressing Lifr+ and Procr+. Sorting and transcriptional profiling of these populations confirmed that they are enriched in adipogenesis genes and are highly related to fibroadipogenic precursors (FAPS). These adipogenic stromal cells (ASC) displayed more adipogenic potential in vitro compared with FAPS, likely due to a more differentiated state. Reduction of ASCs correlated with reduced intramuscular diaphragmatic fat and improved diaphragm function. These data suggest a role for myeloid-derived Spp1 in the differentiation of stromal cells towards an adipogenic fate, leading to accumulation of intramuscular fat in dystrophic muscles.
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