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Although many studies indicate that IFN-I inducers exert favorable effects on broad-spectrum antivirus, immunomodulation, and anti-tumor activities by inducing endogenous IFN-I and IFN-stimulated genes, their function in bone homeostasis still needs further exploration. Here, our study demonstrates 2 distinct IFN-I inducers, diABZI and poly(I:C), as potential therapeutics to alleviate osteolysis and osteoporosis. First, IFN-I inducers suppress the genes that control osteoclast (OC) differentiation and activity in vitro. Moreover, diABZI alleviates bone loss in Ti particle-induced osteolysis and ovariectomized -induced osteoporosis in vivo by inhibiting OC differentiation and function. In addition, the inhibitory effects of IFN-I inducers on OC differentiation are not observed in macrophages derived from Ifnar1\u2212\/\u2212mice, which indicate that the suppressive effect of IFN-I inducers on OC is IFNAR-dependent. Mechanistically, RNAi-mediated silencing of IRF7 and IFIT3 in OC precursors impairs the suppressive effect of the IFN-I inducers on OC differentiation. Taken together, these results demonstrate that IFN-I inducers play a protective role in bone turnover by limiting osteoclastogenesis and bone resorption through the induction of OC-specific mediators via the IFN-I signaling pathway.<\/jats:p>","DOI":"10.1093\/jbmr\/zjae093","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T14:38:19Z","timestamp":1718375899000},"source":"Crossref","is-referenced-by-count":3,"title":["diABZI and poly(I:C) inhibit osteoclastic bone resorption by inducing IRF7 and IFIT3"],"prefix":"10.1093","author":[{"given":"Yingkang","family":"Huang","sequence":"first","affiliation":[{"name":"National Key Laboratory of Immunity and Inflammation , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingchao","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Immunity and Inflammation , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"},{"name":"Department of Orthopedics, The Second Affiliated Hospital of Soochow University , Suzhou 215004, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Zhejiang Provincial People\u2019s Hospital , Hangzhou 310014, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Immunity and Inflammation , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"},{"name":"Department of Orthopedics, The Second Affiliated Hospital of Soochow University , Suzhou 215004, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapei","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Immunity and Inflammation , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zigang","family":"Qiao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Immunity and Inflammation , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiping","family":"Yao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Immunity and Inflammation , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Soochow University , Suzhou 215006, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Affiliated Hospital of Soochow University , Suzhou 215004, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2975-0118","authenticated-orcid":false,"given":"Feng","family":"Ma","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Immunity and Inflammation , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"},{"name":"Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine , and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, , Suzhou 215123, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"issue":"5","key":"2024070808293207800_ref1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41419-020-2548-3","article-title":"QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism","volume":"11","author":"Du","year":"2020","journal-title":"Cell Death Dis"},{"issue":"6937","key":"2024070808293207800_ref2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and 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mimetic","volume":"369","author":"Chin","year":"2020","journal-title":"Science"},{"issue":"59","key":"2024070808293207800_ref42","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abi9002","article-title":"A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection","volume":"6","author":"Humphries","year":"2021","journal-title":"Science Immunol"},{"issue":"59","key":"2024070808293207800_ref43","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abi9007","article-title":"Pharmacological activation of STING blocks SARS-CoV-2 infection","volume":"6","author":"Li","year":"2021","journal-title":"Sci Immunol"},{"issue":"1","key":"2024070808293207800_ref44","doi-asserted-by":"crossref","first-page":"4558","DOI":"10.1038\/s41467-021-24867-2","article-title":"STING suppresses bone cancer pain via immune and neuronal modulation","volume":"12","author":"Wang","year":"2021","journal-title":"Nat 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