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One therapeutic strategy is suppressing the bone resorption function of hyperactive osteoclasts, but there is no effective drug in clinical practice so far. Herein, it is demonstrated that fullerenols suppress the bone resorption of osteoclasts by inhibiting ruffled borders (RBs) formation. The RBs formation, which is supported by well\u2010aligned actin bundles (B\u2010actins), is a critical event for osteoclast bone resorption. To facilitate this function, osteoclast RBs dynamics is regulated by variable microenvironments to bundle F\u2010actins, protrude cell membrane, and so on. B\u2010actin perturbation by fullerenols is determined here, offering an opportunity to regulate osteoclast function by destroying RBs. In vivo, the therapeutic effect of fullerenols on overactive osteoclasts is confirmed in a mouse model of lipopolysaccharide\u2010induced bone erosion. Collectively, the findings suggest that fullerenols adhere to F\u2010actin surfaces and inhibit RBs formation in osteoclasts, mainly through hampering Ca<jats:sup>2+<\/jats:sup> from bundling F\u2010actins, and this is likely due to the stereo\u2010hindrance effect caused by adherent fullerenols.<\/jats:p>","DOI":"10.1002\/smll.201802549","type":"journal-article","created":{"date-parts":[[2018,10,18]],"date-time":"2018-10-18T06:42:03Z","timestamp":1539844923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Highly Dispersed Fullerenols Hamper Osteoclast Ruffled Border Formation by Perturbing Ca<sup>2+<\/sup> Bundles"],"prefix":"10.1002","volume":"14","author":[{"given":"Weihong","family":"Gu","sequence":"first","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterial and Nanosafety Institute of High Energy Physics Chinese Academy of Sciences  Beijing 100049 China"},{"name":"University of 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