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While the modulation of osteoclast activity is well established for preventing bone-related diseases, there is an increasing demand for novel classes of anti-resorption agents. Herein, we investigated non-coding RNA molecules and proposed\n                    <jats:italic>DLEU1<\/jats:italic>\n                    and miR-16 as potential candidates for modulating osteoclast functions.\n                    <jats:italic>DLEU1<\/jats:italic>\n                    and miR-16 target cell fusion at both the early and late stages of osteoclastogenesis but operate through independent pathways.\n                    <jats:italic>DLEU1<\/jats:italic>\n                    silencing hinders the fusion process, leading to abrogation of the phagocytic cup fusion modality and a reduction in the fusion events between mononucleated precursors and multinucleated osteoclasts, while miR-16 influences monocyte-to-osteoclast differentiation, impairing osteoclasts formation but not the number of nuclei at early stages. On the other hand, using these non-coding RNAs to engineer mature osteoclasts has implications for bone resorption. Both\n                    <jats:italic>DLEU1<\/jats:italic>\n                    and miR-16 influence the speed of resorption in pit-forming osteoclasts, without affecting the resorbed area. However, the impact of increasing miR-16 levels extends more broadly, affecting trench-forming osteoclasts as well, leading to a reduction in their percentage, speed, and resorbed area. These findings offer potential new therapeutic targets to ameliorate bone destruction in skeletal diseases.\n                  <\/jats:p>","DOI":"10.1038\/s41419-024-06983-1","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T20:02:01Z","timestamp":1728590521000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Stage-specific modulation of multinucleation, fusion, and resorption by the long non-coding RNA DLEU1 and miR-16 in human primary osteoclasts"],"prefix":"10.1038","volume":"15","author":[{"given":"Sara Reis","family":"Moura","sequence":"first","affiliation":[]},{"given":"Ana Beatriz","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"Jacob Bastholm","family":"Olesen","sequence":"additional","affiliation":[]},{"given":"M\u00e1rio Adolfo","family":"Barbosa","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-314X","authenticated-orcid":false,"given":"Kent","family":"S\u00f8e","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-8587","authenticated-orcid":false,"given":"Maria In\u00eas","family":"Almeida","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"6983_CR1","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-020-00871-9","volume":"16","author":"JA Kanis","year":"2021","unstructured":"Kanis JA, Norton N, Harvey NC, Jacobson T, Johansson H, Lorentzon M, et al. 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