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Developing novel therapeutic drugs about inhibiting excessive osteoclastogenesis acts as an efficient approach to preventing inflammatory bone destruction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To study this, we explored the potential effects and mechanisms of compound 17 on inflammatory osteolysis in vitro. Meanwhile, a lipopolysaccharide (LPS)\u2010induced calvarial osteolysis mouse model was used to evaluate the protective effect of compound 17 on inflammatory bone destruction in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In our study, we found that compound 17 could inhibit osteoclast (OC) differentiation and bone resorption during RANKL and LPS stimulation in a time\u2010 and dose\u2010dependent manner, while compounds 5 and 13 did not have the same effects. Mechanistically, compound 17 promoted phosphatase and tensin homologue (PTEN) activity by reducing PTEN ubiquitination, thereby restraining the RANKL\u2010induced NF\u2010\u03baB pathway, resulting in the inhibition of the expression of osteoclastogenesis\u2010related genes and the formation of the NLRP3 inflammasome. Additionally, we also investigated whether compound 17 could negatively modulate macrophage polarization and repolarization due to its anti\u2010inflammatory effects. Moreover, compound 17 also plays an important role in osteoblast differentiation and mineralization. In vivo experiments showed that compound 17 could effectively protect mice from LPS\u2010induced inflammatory bone destruction by inhibiting osteoclastogenesis and inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these results show that compound 17 might play protective role in inflammatory bone destruction through inhibiting osteoclastogenesis and inflammation. These findings imply a possible role of compound 17 in inflammatory osteolysis\u2010related diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.240","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T08:22:43Z","timestamp":1606897363000},"source":"Crossref","is-referenced-by-count":18,"title":["A selected small molecule prevents inflammatory osteolysis through restraining osteoclastogenesis by modulating PTEN activity"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6975-2874","authenticated-orcid":false,"given":"Yueqi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biomedical Materials Science Third Military Medical University (Army Medical University)  Chongqing PR China"},{"name":"Department of Orthopaedics, Southwest Hospital Third Military Medical University (Army Medical University)  Chongqing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Materials Science Third Military Medical University (Army Medical University)  Chongqing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Materials Science Third Military Medical University (Army Medical University)  Chongqing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Materials Science Third Military Medical University (Army Medical University)  Chongqing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Materials Science Third Military Medical University (Army Medical University)  Chongqing PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products &amp; 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