{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:40:32Z","timestamp":1780926032237,"version":"3.54.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Osteoclasts determine bone tissue turnover. Their increased activity causes osteoporosis, their dysfunction osteopetrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Murine monocytic ER-Hoxb8 cells differentiate into OCs upon treatment with M-CSF and RANKL and upregulate the collagen-binding integrin \u03b12\u03b21 distinctly earlier than other OC markers, such as the OC-associated receptor, OSCAR. Integrin \u03b12\u03b21 promotes OC differentiation at multiple levels by stimulating differentiation-relevant genes, by regulating cell matrix adhesion and the formation of adhesion-promoting protrusions, and by the upregulation of proteins involved in precursor cell fusion. The two key factors in osteoclastogenesis, RANK and NFATc1, were essentially unaffected after knocking out the ITGA2 gene encoding integrin \u03b12 subunit. However, compared to integrin \u03b12\u03b21 expressing ER-Hoxb8 cells, ITGA2-deficient cells adhered differently with more branched filopodia and significantly longer tunneling nanotubes. Despite the higher number of fusion-relevant TNTs, they form fewer syncytia. They also resorb less hydroxyapatite, because integrin \u03b12\u03b21 regulates expression of lacuna proteins necessary for bone matrix resorption. The impaired syncytia formation of ITGA2-deficient OC precursor cells also correlated with reduced gene activation of fusion-supporting DC-STAMP and with an almost abolished transcription of tetraspanin CD9. CD9 only partially colocalized with integrin \u03b12\u03b21 in TNTs and filopodia of integrin \u03b12\u03b21-expressing OC precursors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings define integrin \u03b12\u03b21 as an early marker of OC differentiation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2024.1448725","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T04:45:08Z","timestamp":1723697108000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrin \u03b12 is an early marker for osteoclast differentiation that contributes to key steps in osteoclastogenesis"],"prefix":"10.3389","volume":"12","author":[{"given":"Katrin","family":"Brockhaus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Hemsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia-Larissa","family":"Jauch-Speer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Niland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vogl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes A.","family":"Eble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.gendis.2018.12.003","article-title":"Regulation and functions of integrin \u03b12 in cell adhesion and disease","volume":"6","author":"Adorno-Cruz","year":"2019","journal-title":"Genes Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e8","DOI":"10.4110\/in.2018.18.e8","article-title":"Regulation of osteoclast differentiation by cytokine networks","volume":"18","author":"Amarasekara","year":"2018","journal-title":"Immune Netw."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1002\/jcp.31036","article-title":"Fine-tuning osteoclastogenesis: an insight into the cellular and molecular regulation of osteoclastogenesis","volume":"238","author":"Anwar","year":"2023","journal-title":"J. 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