{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:08:19Z","timestamp":1792872499878,"version":"4.5.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T00:00:00Z","timestamp":1492992000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2017,6]]},"DOI":"10.1038\/nm.4324","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T11:04:25Z","timestamp":1493031865000},"page":"775-781","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1432,"title":["Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment"],"prefix":"10.1038","volume":"23","author":[{"given":"Ok Hee","family":"Jeon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaekyu","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remi-Martin","family":"Laberge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8429-4813","authenticated-orcid":false,"given":"Marco","family":"Demaria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sona","family":"Rathod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain P","family":"Vasserot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Wook","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Hun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Poon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"David","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren J","family":"Baker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M","family":"van Deursen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Campisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer H","family":"Elisseeff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,24]]},"reference":[{"key":"BFnm4324_CR1","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1146\/annurev-physiol-030212-183653","volume":"75","author":"J Campisi","year":"2013","unstructured":"Campisi, J. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75, 685\u2013705 (2013).","journal-title":"Annu. Rev. Physiol."},{"key":"BFnm4324_CR2","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/nature13193","volume":"509","author":"JM van Deursen","year":"2014","unstructured":"van Deursen, J.M. The role of senescent cells in ageing. Nature 509, 439\u2013446 (2014).","journal-title":"Nature"},{"key":"BFnm4324_CR3","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.cell.2005.02.003","volume":"120","author":"J Campisi","year":"2005","unstructured":"Campisi, J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513\u2013522 (2005).","journal-title":"Cell"},{"key":"BFnm4324_CR4","doi-asserted-by":"publisher","first-page":"2853","DOI":"10.1371\/journal.pbio.0060301","volume":"6","author":"JP Copp\u00e9","year":"2008","unstructured":"Copp\u00e9, J.P. et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 6, 2853\u20132868 (2008).","journal-title":"PLoS Biol."},{"key":"BFnm4324_CR5","first-page":"183","volume":"14","author":"J Campisi","year":"2000","unstructured":"Campisi, J. Cancer, aging and cellular senescence. In Vivo 14, 183\u2013188 (2000).","journal-title":"In Vivo"},{"key":"BFnm4324_CR6","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1111\/j.1474-9726.2012.00795.x","volume":"11","author":"G Nelson","year":"2012","unstructured":"Nelson, G. et al. A senescent cell bystander effect: senescence-induced senescence. Aging Cell 11, 345\u2013349 (2012).","journal-title":"Aging Cell"},{"key":"BFnm4324_CR7","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature10600","volume":"479","author":"DJ Baker","year":"2011","unstructured":"Baker, D.J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232\u2013236 (2011).","journal-title":"Nature"},{"key":"BFnm4324_CR8","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/nature16932","volume":"530","author":"DJ Baker","year":"2016","unstructured":"Baker, D.J. et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature 530, 184\u2013189 (2016).","journal-title":"Nature"},{"key":"BFnm4324_CR9","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1038\/ncb1744","volume":"10","author":"DJ Baker","year":"2008","unstructured":"Baker, D.J. et al. Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. Nat. Cell Biol. 10, 825\u2013836 (2008).","journal-title":"Nat. Cell Biol."},{"key":"BFnm4324_CR10","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nrd1693","volume":"4","author":"HA Wieland","year":"2005","unstructured":"Wieland, H.A., Michaelis, M., Kirschbaum, B.J. & Rudolphi, K.A. Osteoarthritis\u2014an untreatable disease? Nat. Rev. Drug Discov. 4, 331\u2013344 (2005).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnm4324_CR11","first-page":"479","volume":"41","author":"JA Martin","year":"2004","unstructured":"Martin, J.A., Brown, T., Heiner, A. & Buckwalter, J.A. Post-traumatic osteoarthritis: the role of accelerated chondrocyte senescence. Biorheology 41, 479\u2013491 (2004).","journal-title":"Biorheology"},{"key":"BFnm4324_CR12","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1046\/j.1474-9728.2002.00008.x","volume":"1","author":"JS Price","year":"2002","unstructured":"Price, J.S. et al. The role of chondrocyte senescence in osteoarthritis. Aging Cell 1, 57\u201365 (2002).","journal-title":"Aging Cell"},{"key":"BFnm4324_CR13","doi-asserted-by":"publisher","first-page":"R58","DOI":"10.1186\/ar4494","volume":"16","author":"D Philipot","year":"2014","unstructured":"Philipot, D. et al. p16INK4a and its regulator miR-24 link senescence and chondrocyte terminal differentiation\u2013associated matrix remodeling in osteoarthritis. Arthritis Res. Ther. 16, R58 (2014).","journal-title":"Arthritis Res. Ther."},{"key":"BFnm4324_CR14","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1111\/acel.12562","volume":"16","author":"K McCulloch","year":"2017","unstructured":"McCulloch, K., Litherland, G.J. & Rai, T.S. Cellular senescence in osteoarthritis pathology. Aging Cell 16, 210\u2013218 (2017).","journal-title":"Aging Cell"},{"key":"BFnm4324_CR15","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1016\/j.devcel.2014.11.012","volume":"31","author":"M Demaria","year":"2014","unstructured":"Demaria, M. et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31, 722\u2013733 (2014).","journal-title":"Dev. Cell"},{"key":"BFnm4324_CR16","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/nm.4010","volume":"22","author":"J Chang","year":"2016","unstructured":"Chang, J. et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat. Med. 22, 78\u201383 (2016).","journal-title":"Nat. Med."},{"key":"BFnm4324_CR17","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.molcel.2009.09.021","volume":"36","author":"PD Adams","year":"2009","unstructured":"Adams, P.D. Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence. Mol. Cell 36, 2\u201314 (2009).","journal-title":"Mol. Cell"},{"key":"BFnm4324_CR18","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nrc3960","volume":"15","author":"NE Sharpless","year":"2015","unstructured":"Sharpless, N.E. & Sherr, C.J. Forging a signature of in vivo senescence. Nat. Rev. Cancer 15, 397\u2013408 (2015).","journal-title":"Nat. Rev. Cancer"},{"key":"BFnm4324_CR19","doi-asserted-by":"publisher","first-page":"146","DOI":"10.2152\/jmi.51.146","volume":"51","author":"N Ohtani","year":"2004","unstructured":"Ohtani, N., Yamakoshi, K., Takahashi, A. & Hara, E. The p16INK4a\u2013RB pathway: molecular link between cellular senescence and tumor suppression. J. Med. Invest. 51, 146\u2013153 (2004).","journal-title":"J. Med. Invest."},{"key":"BFnm4324_CR20","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1101\/gad.235184.113","volume":"28","author":"R Salama","year":"2014","unstructured":"Salama, R., Sadaie, M., Hoare, M. & Narita, M. Cellular senescence and its effector programs. Genes Dev. 28, 99\u2013114 (2014).","journal-title":"Genes Dev."},{"key":"BFnm4324_CR21","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1111\/j.1365-2567.2007.02662.x","volume":"122","author":"U Holmlund","year":"2007","unstructured":"Holmlund, U. et al. The novel inflammatory cytokine high mobility group box protein 1 (HMGB1) is expressed by human term placenta. Immunology 122, 430\u2013437 (2007).","journal-title":"Immunology"},{"key":"BFnm4324_CR22","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1083\/jcb.201206006","volume":"201","author":"AR Davalos","year":"2013","unstructured":"Davalos, A.R. et al. p53-dependent release of alarmin HMGB1 is a central mediator of senescent phenotypes. J. Cell Biol. 201, 613\u2013629 (2013).","journal-title":"J. Cell Biol."},{"key":"BFnm4324_CR23","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/nrrheum.2010.159","volume":"6","author":"J Sellam","year":"2010","unstructured":"Sellam, J. & Berenbaum, F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat. Rev. Rheumatol. 6, 625\u2013635 (2010).","journal-title":"Nat. Rev. Rheumatol."},{"key":"BFnm4324_CR24","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1242\/jcs.00912","volume":"117","author":"GP Dowthwaite","year":"2004","unstructured":"Dowthwaite, G.P. et al. The surface of articular cartilage contains a progenitor cell population. J. Cell Sci. 117, 889\u2013897 (2004).","journal-title":"J. Cell Sci."},{"key":"BFnm4324_CR25","doi-asserted-by":"publisher","first-page":"167ra6","DOI":"10.1126\/scitranslmed.3004838","volume":"5","author":"B Sharma","year":"2013","unstructured":"Sharma, B. et al. Human cartilage repair with a photoreactive adhesive\u2013hydrogel composite. Sci. Transl. Med. 5, 167ra6 (2013).","journal-title":"Sci. Transl. Med."},{"key":"BFnm4324_CR26","doi-asserted-by":"publisher","first-page":"e727","DOI":"10.1038\/cddis.2013.199","volume":"4","author":"RM Laberge","year":"2013","unstructured":"Laberge, R.M. et al. Mitochondrial DNA damage induces apoptosis in senescent cells. Cell Death Dis. 4, e727 (2013).","journal-title":"Cell Death Dis."},{"key":"BFnm4324_CR27","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1097\/BOR.0b013e328349c2b1","volume":"23","author":"MB Goldring","year":"2011","unstructured":"Goldring, M.B. & Otero, M. Inflammation in osteoarthritis. Curr. Opin. Rheumatol. 23, 471\u2013478 (2011).","journal-title":"Curr. Opin. Rheumatol."},{"key":"BFnm4324_CR28","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/nrrheum.2012.130","volume":"8","author":"DB Burr","year":"2012","unstructured":"Burr, D.B. & Gallant, M.A. Bone remodelling in osteoarthritis. Nat. Rev. Rheumatol. 8, 665\u2013673 (2012).","journal-title":"Nat. Rev. Rheumatol."},{"key":"BFnm4324_CR29","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/acel.12445","volume":"15","author":"Y Zhu","year":"2016","unstructured":"Zhu, Y. et al. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell 15, 428\u2013435 (2016).","journal-title":"Aging Cell"},{"key":"BFnm4324_CR30","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1002\/jcb.22994","volume":"112","author":"T Komori","year":"2011","unstructured":"Komori, T. Signaling networks in RUNX2-dependent bone development. J. Cell. Biochem. 112, 750\u2013755 (2011).","journal-title":"J. Cell. Biochem."},{"key":"BFnm4324_CR31","doi-asserted-by":"publisher","first-page":"176ra34","DOI":"10.1126\/scitranslmed.3005409","volume":"5","author":"MZ Ruan","year":"2013","unstructured":"Ruan, M.Z. et al. Proteoglycan 4 expression protects against the development of osteoarthritis. Sci. Transl. Med. 5, 176ra34 (2013).","journal-title":"Sci. Transl. Med."},{"key":"BFnm4324_CR32","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1002\/art.33388","volume":"64","author":"RF Loeser","year":"2012","unstructured":"Loeser, R.F. et al. Microarray analysis reveals age-related differences in gene expression during the development of osteoarthritis in mice. Arthritis Rheum. 64, 705\u2013717 (2012).","journal-title":"Arthritis Rheum."},{"key":"BFnm4324_CR33","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.joca.2009.03.002","volume":"17","author":"RF Loeser","year":"2009","unstructured":"Loeser, R.F. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis Cartilage 17, 971\u2013979 (2009).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFnm4324_CR34","doi-asserted-by":"publisher","first-page":"4397","DOI":"10.1073\/pnas.052716199","volume":"99","author":"I Sekiya","year":"2002","unstructured":"Sekiya, I., Vuoristo, J.T., Larson, B.L. & Prockop, D.J. In vitro cartilage formation by human adult stem cells from bone marrow stroma defines the sequence of cellular and molecular events during chondrogenesis. Proc. Natl. Acad. Sci. USA 99, 4397\u20134402 (2002).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"Suppl. 3","key":"BFnm4324_CR35","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","volume":"18","author":"SS Glasson","year":"2010","unstructured":"Glasson, S.S., Chambers, M.G., Van Den Berg, W.B. & Little, C.B. The OARSI histopathology initiative\u2014recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis Cartilage 18 (Suppl. 3), S17\u2013S23 (2010).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFnm4324_CR36","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0924-977X(96)00031-4","volume":"6","author":"S Schreiber","year":"1996","unstructured":"Schreiber, S., Backer, M.M., Yanai, J. & Pick, C.G. The antinociceptive effect of fluvoxamine. Eur. Neuropsychopharmacol. 6, 281\u2013284 (1996).","journal-title":"Eur. Neuropsychopharmacol."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm.4324.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm.4324","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/nm.4324","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nm.4324.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T19:01:25Z","timestamp":1684436485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm.4324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,24]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["BFnm4324"],"URL":"https:\/\/doi.org\/10.1038\/nm.4324","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727547591.793532453","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.727547591.793533895","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.727547591.793533560","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.727547591.793541485","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.727547591.793532953","asserted-by":"object"}]},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,24]]},"assertion":[{"value":"9 December 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"J.C., R.-M.L., Y.P., D.J.B. , J.M.v.D. , M.D., N.D. and J.H.E. own equity in Unity Biotechnology. Johns Hopkins University and Unity Biotechnology own intellectual property related to the research. O.H.J., C.K. and J.H.E. are inventors of Johns Hopkins University intellectual property licensed to Unity Biotechnology.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}