{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:06:34Z","timestamp":1793142394832,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T00:00:00Z","timestamp":1711843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Senescent cells increase in many tissues with age and induce age\u2010related pathologies, including osteoarthritis (OA). Senescent chondrocytes (SnCs) are found in OA cartilage, and the clearance of those chondrocytes prevents OA progression. However, targeting SnCs is challenging due to the absence of a senescent chondrocyte\u2010specific marker. Therefore, we used flow cytometry to screen and select senescent chondrocyte surface markers and cross\u2010validated with published transcriptomic data. Chondrocytes expressing dipeptidyl peptidase\u20104 (DPP\u20104), the selected senescent chondrocyte\u2010specific marker, had multiple senescence phenotypes, such as increased senescence\u2010associated\u2010galactosidase, p16, p21, and senescence\u2010associated secretory phenotype expression, and showed OA chondrocyte phenotypes. To examine the effects of DPP\u20104 inhibition on DPP\u20104+ SnCs, sitagliptin, a DPP\u20104 inhibitor, was treated in\u00a0vitro. As a result, DPP\u20104 inhibition selectively eliminates DPP\u20104+ SnCs without affecting DPP\u20104\u2010 chondrocytes. To assess in\u00a0vivo therapeutic efficacy of targeting DPP\u20104+ SnCs, three known senolytics (ABT263, 17DMAG, and metformin) and sitagliptin were comparatively verified in a DMM\u2010induced rat OA model. Sitagliptin treatment specifically and effectively eliminated DPP\u20104+ SnCs, compared to the other three senolytics. Furthermore, Intra\u2010articular sitagliptin injection to the rat OA model increased collagen type II and proteoglycan expression and physical functions and decreased cartilage destruction, subchondral bone plate thickness and MMP13 expression, leading to the amelioration of OA phenotypes. Collectively, OARSI score was lowest in the sitagliptin treatment group. Taken together, we verified DPP\u20104 as a surface marker for SnCs and suggested that the selective targeting of DPP\u20104+ chondrocytes could be a promising strategy to prevent OA progression.<\/jats:p>","DOI":"10.1111\/acel.14161","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T02:10:00Z","timestamp":1711937400000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Selective targeting of dipeptidyl\u2010peptidase 4 (DPP\u20104) positive senescent chondrocyte ameliorates osteoarthritis progression"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6199-908X","authenticated-orcid":false,"given":"Du Hyun","family":"Ro","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Seoul National University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0773-8373","authenticated-orcid":false,"given":"Gun Hee","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Seoul National University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-9331","authenticated-orcid":false,"given":"Ji Yoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Seoul National University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9621-0739","authenticated-orcid":false,"given":"Seong Ki","family":"Min","sequence":"additional","affiliation":[{"name":"Laboratory for Cellular Response to Oxidative Stress Cell2in, Inc.  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Ru","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Seoul National University Hospital  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Jung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Seoul National University Hospital  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Young","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Seoul National University Hospital  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Seoul National University Hospital  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung 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