{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:15:53Z","timestamp":1791731753527,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T00:00:00Z","timestamp":1549843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Puglia (Italy)","award":["QZYCUM0"],"award-info":[{"award-number":["QZYCUM0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast\/osteoclast ratio. The behavior of ion channels in the presence of BPs is not known. To investigate this, the effect of zoledronic acid BP (ZOL) (3 \u00d7 10\u22128 to 5 \u00d7 10\u22124 M) treatment, on ion channels, cell proliferation, and mineralization, has been investigated on preosteoclast-like cells, RAW264.7, preosteoblast-like cells MC3T3-E1, and rat\/mouse native bone marrow-derived osteoblasts. In whole-cell patch clamp on cell line- and bone marrow-derived osteoblasts, ZOL potentiated outward currents. On RAW264.7, ZOL (10\u22124 M)-evoked current was reduced by the Kv channel blocker tetraethylammonium hydrochloride (TEA), but not by the selective TRPV1-channel antagonist capsazepine. On MC3T3-E1 cells and bone marrow-derived osteoblasts, ZOL-evoked current (5 \u00d7 10\u22128 to 10\u22124 M) was reduced by capsazepine, whereas the selective TRPV1-channel agonist capsaicin potentiated the control current. In the cell proliferation assay, 72 h incubation of RAW264.7 and MC3T3-E1 cells with ZOL reduced proliferation, with IC50 values of 2.62 \u00d7 10\u22127 M and 2.02 \u00d7 10\u22125 M, respectively. Mineralization of MC3T3-E1 cells and bone marrow-derived osteoblasts was observed in the presence of capsaicin and ZOL (5 \u00d7 10\u22128\u201310\u22127 M); ZOL effects were antagonized by capsazepine. In summary, the ZOL-induced activation of TRPV1 channel mediates the mineralization of osteoblasts and counterbalances the antiproliferative effects, increasing the IC50. This mechanism is not operative in osteoclasts lacking the TRPV1 channel.<\/jats:p>","DOI":"10.3390\/cancers11020206","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T03:18:20Z","timestamp":1549941500000},"page":"206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Zoledronic Acid Modulation of TRPV1 Channel Currents in Osteoblast Cell Line and Native Rat and Mouse Bone Marrow-Derived Osteoblasts: Cell Proliferation and Mineralization Effect"],"prefix":"10.3390","volume":"11","author":[{"given":"Rosa","family":"Scala","sequence":"first","affiliation":[{"name":"Section of Pharmacology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, I-70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Maqoud","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, I-70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariacristina","family":"Angelelli","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, I-70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-5795","authenticated-orcid":false,"given":"Ramon","family":"Latorre","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Centro Interdisciplinario de Neurociencia de Valpara\u00edso, Universidad de Valpara\u00edso, Valpara\u00edso 2366103, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Perrone","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Section, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, I-70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Scilimati","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Section, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, I-70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Tricarico","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, I-70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/bcr2781","article-title":"Breast cancer metastasis to the bone: Mechanisms of bone loss","volume":"12","author":"Chen","year":"2010","journal-title":"Breast Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1158\/1078-0432.CCR-13-1590","article-title":"Molecular mechanisms of bone metastasis and associated muscle weakness","volume":"20","author":"Waning","year":"2014","journal-title":"Clin. 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