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ResearchIn-Press PreviewAgingBone biology Open Access | 10.1172/JCI179834
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Saul, D. in: JCI | PubMed | Google Scholar |
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Doolittle, M. in: JCI | PubMed | Google Scholar |
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Rowsey, J. in: JCI | PubMed | Google Scholar
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Froemming, M. in: JCI | PubMed | Google Scholar
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Kosinsky, R. in: JCI | PubMed | Google Scholar
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Vos, S. in: JCI | PubMed | Google Scholar
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Ruan, M. in: JCI | PubMed | Google Scholar
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
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1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Chandra, A. in: JCI | PubMed | Google Scholar
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Pignolo, R. in: JCI | PubMed | Google Scholar
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
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1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Farr, J. in: JCI | PubMed | Google Scholar |
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
Find articles by Monroe, D. in: JCI | PubMed | Google Scholar |
1Division of Endocrinology, Mayo Clinic, Rochester, United States of America
2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States of America
3Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, United States of America
4Division of Endocrinology, Mayo Cinic, Rochester, United States of America
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Published May 16, 2024 - More info
Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21+ cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21+ cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21+ cell clearance did not alter bone loss due to aging; conversely, p16+ cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21+ neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21+ OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell-like OCH subset that was p21+ and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells were key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings established contextual roles of p21+ vs p16+ senescent/senescent-like cells that may be leveraged for therapeutic opportunities.