ArticleThe Journal of clinical investigation2022
Age-associated callus senescent cells produce TGF-β1 that inhibits fracture healing in aged mice.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Association between platelet to lymphocyte ratio and the risk of vertebral fracture in patients with osteoporosis: a systematic review and meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Loss of EGFR activity in skeletal stem/progenitor cells is associated with impaired fracture healing in aged mice.Bioactive materials · 2027Article
- Skeletal stem and progenitor cell niche organization, regulation and repair.Reviews in endocrine & metabolic disorders · 2026Review
- Ganoderic acid A accelerates osteoporotic fracture healing by promoting osteogenic differentiation via estrogen receptor alpha binding.Journal of orthopaedic translation · 2026Article
- Youthfulness of marrow AdipoqBone research · 2026Article
- Cellular Senescence and the SASP in HFpEF: Pathogenic Mechanisms and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Transcription-independent induction of rapid-onset senescence is integral to healing.Nature cell biology · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Engineered human plasma-derived cryogels as a multifunctional scaffold to promote diabetic wound healing.Materials today. Bio · 2026Article
- Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.Biomolecules · 2026Review
- Quercetin-loaded composite materials for bone regeneration: a review of carriers, controlled release, and mechanistic advances.Stem cell research & therapy · 2026Review
- A spatiotemporal atlas of senescence-associated secretory phenotype in fracture healing: stage-dependent mechanisms and therapeutic windows.Inflammation and regeneration · 2026Review
- MST4 as a key driver of osteoclast activation in osteoporosis.Journal of pharmaceutical analysis · 2026Article
- Co-Treatment With rhBMP-2 and Rapamycin Modulates Osteogenesis-Adipogenesis Balance to Enhance Aged Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Supramolecular delivery of senolytics enables targeted anti-senescence therapy and accelerated fracture healing.Journal of nanobiotechnology · 2026Article
- Megakaryocytic TGFβ1 orchestrates osteogenesis of LepRExperimental & molecular medicine · 2026Article
- The Effect of Age and Use of Enamel Matrix Derivative on Implant Loss.Dentistry journal · 2026Article
- Spatial multi-omics decoding of the fracture nonunion niche: from immune-vascular-skeletal crosstalk to precision regeneration.Frontiers in medicine · 2026Review
- Cellular senescence in musculoskeletal diseases: biological mechanisms and clinical implications.Theranostics · 2026Review
- Article
19 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 2 countries.
Funding
Abstract
Cellular senescence plays an important role in human diseases, including osteoporosis and osteoarthritis. Senescent cells (SCs) produce the senescence-associated secretory phenotype to affect the function of neighboring cells and SCs themselves. Delayed fracture healing is common in the elderly and is accompanied by reduced mesenchymal progenitor cells (MPCs). However, the contribution of cellular senescence to fracture healing in the aged has not to our knowledge been studied. Here, we used C57BL/6J 4-month-old young and 20-month-old aged mice and demonstrated a rapid increase in SCs in the fracture callus of aged mice. The senolytic drugs dasatinib plus quercetin enhanced fracture healing in aged mice. Aged callus SCs inhibited the growth and proliferation of callus-derived MPCs (CaMPCs) and expressed high levels of TGF-β1. TGF-β-neutralizing Ab prevented the inhibitory effects of aged callus SCs on CaMPCs and promoted fracture healing in aged mice, which was associated with increased CaMPCs and proliferating cells. Thus, fracture triggered a significant cellular senescence in the callus cells of aged mice, which inhibited MPCs by expressing TGF-β1. Short-term administration of dasatinib plus quercetin depleted callus SCs and accelerated fracture healing in aged mice. Senolytic drugs represent a promising therapy, while TGF-β1 signaling is a molecular mechanism for fractures in the elderly via SCs.
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