{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:15:12Z","timestamp":1779909312743,"version":"3.53.1"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1180495"],"award-info":[{"award-number":["1180495"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Zoledronic acid, the most frequent agent associated with bisphosphonate\u2010related osteonecrosis of the jaw (BRONJ), has been reported as cytotoxic for bone and vascular cells. Hence, identification of novel approaches aiming to counteract its cytotoxic effects will be desirable to develop preventive therapies for BRONJ. The salivary peptide Histatin\u20101 was recently shown to promote oral wound healing, by acting in epithelial and endothelial cells; however, its effects on cells exposed to zoledronic acid have not been explored. This study aims to unveil the role of Histatin\u20101 in osteoblastic and vascular cell lineages challenged with zoledronic acid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effects of zoledronic acid (1\u2013100\u00a0\u00b5M), Histatin\u20101 (10\u00a0\u00b5M), or their combination was evaluated in cytotoxicity (Trypan Blue exclusion) and cell migration (Boyden Chamber) assays. Caspase\u20103 cleavage was evaluated by Western blot. The angiogenic capacity of endothelial cells was assessed in a tubule formation assay <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Zoledronic acid decreased cell viability and migration of osteosarcoma cells (SAOS\u20102) and preosteoblasts (MC3T3\u2010E1), in a dose\u2010response manner. Importantly, Histatin\u20101 restored both cell viability and migration in both cell lines upon challenge with zoledronic acid. These effects were recapitulated in endothelial cells (EA.hy926), as Histatin\u20101 counteracted cytotoxic and antimigratory effects of zoledronic acid, and restored the angiogenic capacity <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conclude that Histatin\u20101 counteracts the cytotoxic and antimigratory effects of zoledronic acid in osteoblast\u2010like and endothelial cells. These observations highlight the potential use of Histatin\u20101, in the design of novel therapies aiming to prevent and treat BRONJ.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.18-0644","type":"journal-article","created":{"date-parts":[[2019,1,28]],"date-time":"2019-01-28T21:36:19Z","timestamp":1548711379000},"page":"766-774","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Histatin\u20101 counteracts the cytotoxic and antimigratory effects of zoledronic acid in endothelial and osteoblast\u2010like cells"],"prefix":"10.1002","volume":"90","author":[{"given":"Mart\u00edn","family":"Castro","sequence":"first","affiliation":[{"name":"Faculty of Dentistry Institute for Research in Dental Sciences, Universidad de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Torres","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry Institute for Research in 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