{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:28:59Z","timestamp":1790882939485,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["357\/18"],"award-info":[{"award-number":["357\/18"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cherubism is a rare autosomal dominant bone disease of the maxilla and mandible with variable severity. Most patients harbor a mutation in SH3 domain-binding protein 2 (SH3BP2), yet factors influencing genetic penetrance and clinical severity remain unclear. In mice, this mutation induces tumor necrosis factor alpha (TNF-\u03b1)-mediated systemic inflammation, though its role in human cherubism is debated. Multinucleated osteoclasts (OCs), rather than macrophages, are linked to symptom severity, but whether this results from progenitor differentiation or environmental factors is unknown. To elucidate this, OC differentiation and resorption were compared in PBMCs from two symptomatic and one asymptomatic carrier of the same cherubism mutation. All carriers exhibited larger OCs than healthy controls when cultured with RANKL or TNF-\u03b1. On bone slices, OCs from carriers resorbed more bone than controls, with TNF-\u03b1 exerting a weaker effect than RANKL. No significant differences were observed between symptomatic and asymptomatic carriers, suggesting that symptom severity is influenced by microenvironmental factors external to OCs. Additionally, while TNF-\u03b1 promotes giant cell formation in cherubism OCs, its impact on resorption is limited. These findings may explain why TNF-\u03b1 inhibition reduces giant cell numbers in cherubism lesions without improving clinical outcomes.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziaf148","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T13:56:18Z","timestamp":1757426178000},"source":"Crossref","is-referenced-by-count":1,"title":["Comparative analysis of osteoclast function in symptomatic and asymptomatic individuals with cherubism-causing SH3BP2 mutation"],"prefix":"10.1093","volume":"9","author":[{"given":"Chen","family":"Abramovitch-Dahan","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva , 8410500,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Katchkovsky","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion 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Bar","family":"Droma","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Unit, Soroka Medical Center , Beer-Sheva , 8410101,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navot","family":"Givol","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Unit, Soroka Medical Center , Beer-Sheva , 8410101,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Geftler","sequence":"additional","affiliation":[{"name":"Orthopedic Surgery Department, Soroka Medical Center , Beer-Sheva , 8457108,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9039-5565","authenticated-orcid":false,"given":"Merav","family":"Fraenkel","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Ben-Gurion University and Soroka Medical Center , Beer-Sheva , 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