{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T09:28:04Z","timestamp":1781602084151,"version":"3.54.5"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008896","name":"Wolfson Family Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008896","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Zoledronic acid (Zol) is a potent bisphosphonate that inhibits the differentiation of monocytes into osteoclasts. It is often used in combination with dexamethasone (Dex), a glucocorticoid that promotes the resolution of inflammation, to treat malignant diseases, such as multiple myeloma. This treatment can result in bone pathologies, namely medication related osteonecrosis of the jaw, with a poor understanding of the molecular mechanism on monocyte differentiation. IFN-\u03b2 is a pro-resolving cytokine well-known as an osteoclast differentiation inhibitor. Here, we explored whether Zol and\/or Dex regulate macrophage osteoclastic differentiation <jats:italic>via<\/jats:italic> IFN-\u03b2. RAW 264.7 and peritoneal macrophages were treated with Zol and\/or Dex for 4\u201324\u00a0h, and IFN-\u03b2 secretion was examined by ELISA, while the IFN stimulated gene (ISG) 15 expression was evaluated by Western blotting. RANKL-induced osteoclastogenesis of RAW 264.7 cells was determined by TRAP staining following treatment with Zol+Dex or IFN-\u03b2 and anti-IFN-\u03b2 antibodies. We found only the combination of Zol and Dex increased IFN-\u03b2 secretion by RAW 264.7 macrophages at 4\u00a0h and, correspondingly, ISG15 expression in these cells at 24\u00a0h. Moreover, Zol+Dex blocked osteoclast differentiation to a similar extent as recombinant IFN-\u03b2. Neutralizing anti-IFN-\u03b2 antibodies reversed the effect of Zol+Dex on ISG15 expression and partially recovered osteoclastic differentiation induced by each drug alone or in combination. Finally, we found Zol+Dex also induced IFN-\u03b2 expression in peritoneal resolution phase macrophages, suggesting these drugs might be used to enhance the resolution of acute inflammation. Altogether, our findings suggest Zol+Dex block the differentiation of osteoclasts through the expression of IFN-\u03b2. Revealing the molecular pathway behind this regulation may lead to the development of IFN-\u03b2-based therapy to inhibit osteoclastogenesis in multiple myeloma patients.<\/jats:p>","DOI":"10.3389\/fphar.2022.1002550","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T05:27:45Z","timestamp":1665725265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["IFN-\u03b2 mediates the anti-osteoclastic effect of bisphosphonates and dexamethasone"],"prefix":"10.3389","volume":"13","author":[{"given":"Prajakta","family":"Kalkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gal","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Tamari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagie","family":"Schif-Zuck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadar","family":"Zigdon-Giladi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amiram","family":"Ariel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/s41419-018-0332-4","article-title":"Glucocorticoids promote apoptosis of proinflammatory monocytes by inhibiting ERK activity","volume":"9","author":"Achuthan","year":"2018","journal-title":"Cell. 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