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Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21\n                    <jats:sup>+<\/jats:sup>\n                    cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21\n                    <jats:sup>+<\/jats:sup>\n                    cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21\n                    <jats:sup>+<\/jats:sup>\n                    cell clearance did not alter bone loss due to aging; conversely, p16\n                    <jats:sup>+<\/jats:sup>\n                    cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21\n                    <jats:sup>+<\/jats:sup>\n                    neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21\n                    <jats:sup>+<\/jats:sup>\n                    OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell\u2013like OCH subset that was p21\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    versus p16\n                    <jats:sup>+<\/jats:sup>\n                    senescent\/senescent-like cells that may be leveraged for therapeutic opportunities.\n                  <\/jats:p>","DOI":"10.1172\/jci179834","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T12:00:20Z","timestamp":1715860820000},"source":"Crossref","is-referenced-by-count":44,"title":["Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-3710","authenticated-orcid":true,"given":"Dominik","family":"Saul","sequence":"first","affiliation":[{"name":"Division of Endocrinology and"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA."},{"name":"Department of Trauma and Reconstructive Surgery, BG Clinic, University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0912-0095","authenticated-orcid":true,"given":"Madison L.","family":"Doolittle","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Rowsey","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell N.","family":"Froemming","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn L.","family":"Kosinsky","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA."},{"name":"Robert Bosch Center for Tumor Diseases, Stuttgart, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J.","family":"Vos","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Ruan","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and"},{"name":"Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2002-0418","authenticated-orcid":true,"given":"Nathan 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