ArticleAging cell2020
Geriatric fragility fractures are associated with a human skeletal stem cell defect.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 30 citations in OpenAlex.
- Skeletal stem and progenitor cell niche organization, regulation and repair.Reviews in endocrine & metabolic disorders · 2026Review
- miR-205a mediated suppression of CDH11 disrupts Wnt/β-catenin signaling and impairs chondrocyte differentiation.Cell death discovery · 2026Article
- The puzzling duality of mesenchymal stem cells and adipocytes in bone marrow and ageing.npj aging · 2026Review
- Inflammation-responsive biomimetic hybrid nanovesicles reverse stem cell senescence by up-regulating SIRT1 to treat periodontitis.Journal of nanobiotechnology · 2026Article
- Taurine transporter SLC6A6 expression promotes mesenchymal stromal cell function.Cell death & disease · 2026Article
- Article
- Human skeletal development and regeneration are shaped by functional diversity of stem cells across skeletal sites.Cell stem cell · 2025Article
- Skeletal stem and progenitor cells in bone physiology, ageing and disease.Nature reviews. Endocrinology · 2025Review
- Characterization of human skeletal stem cells in closed and open tibia fractures: a single center pilot study.Frontiers in physiology · 2025Article
- New evidence for the epigenetic regulation of skeletal stem cells.Science bulletin · 2024Article
- New insights into the properties, functions, and aging of skeletal stem cells.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Review
- Purification and functional characterization of novel human skeletal stem cell lineages.Nature protocols · 2023Review
- Turning the spotlight on bone marrow adipocytes in haematological malignancy and non-malignant conditions.British journal of haematology · 2023Review
- Biomarkers of aging.Science China. Life sciences · 2023Review
- Differential regulation of skeletal stem/progenitor cells in distinct skeletal compartments.Frontiers in physiology · 2023Review
- Revolutionizing bone regeneration: advanced biomaterials for healing compromised bone defects.Frontiers in aging · 2023Review
- Role of endocrine PACAP in age-related diseases.Frontiers in endocrinology · 2023Review
- The landscape of aging.Science China. Life sciences · 2022Review
- Cross-species comparisons reveal resistance of human skeletal stem cells to inhibition by non-steroidal anti-inflammatory drugs.Frontiers in endocrinology · 2022Article
- Aging of Skeletal Stem Cells.Advances in geriatric medicine and research · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
Fragility fractures have a limited capacity to regenerate, and impaired fracture healing is a leading cause of morbidity in the elderly. The recent identification of a highly purified bona fide human skeletal stem cell (hSSC) and its committed downstream progenitor cell populations provides an opportunity for understanding the mechanism of age-related compromised fracture healing from the stem cell perspective. In this study, we tested whether hSSCs isolated from geriatric fractures demonstrate intrinsic functional defects that drive impaired healing. Using flow cytometry, we analyzed and isolated hSSCs from callus tissue of five different skeletal sites (n = 61) of patients ranging from 13 to 94 years of age for functional and molecular studies. We observed that fracture-activated amplification of hSSC populations was comparable at all ages. However, functional analysis of isolated stem cells revealed that advanced age significantly correlated with reduced osteochondrogenic potential but was not associated with decreased in vitro clonogenicity. hSSCs derived from women displayed an exacerbated functional decline with age relative to those of aged men. Transcriptomic comparisons revealed downregulation of skeletogenic pathways such as WNT and upregulation of senescence-related pathways in young versus older hSSCs. Strikingly, loss of Sirtuin1 expression played a major role in hSSC dysfunction but re-activation by trans-resveratrol or a small molecule compound restored in vitro differentiation potential. These are the first findings that characterize age-related defects in purified hSSCs from geriatric fractures. Our results provide a foundation for future investigations into the mechanism and reversibility of skeletal stem cell aging in humans.
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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.