Suppression of IRF9 Promotes Osteoclast Differentiation by Decreased Ferroptosis via STAT3 Activation
Osteoporosis is a chronic disease that endangers the health of the elderly. Inhibiting osteoclast hyperactivity is a key aspect of osteoporosis prevention and treatment. Several studies have shown that interferon regulatory factor 9 (IRF9) not only regulates innate and adaptive immune responses but...
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| Veröffentlicht in: | Inflammation 2024-02, Vol.47 (1), p.99-113 |
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| creator | Lan, Chao Zhou, Xuan Shen, Ximei Lin, Youfen Chen, Xiaoyuan Lin, Jiebin Zhang, Yongze Zheng, Lifeng Yan, Sunjie |
| description | Osteoporosis is a chronic disease that endangers the health of the elderly. Inhibiting osteoclast hyperactivity is a key aspect of osteoporosis prevention and treatment. Several studies have shown that interferon regulatory factor 9 (IRF9) not only regulates innate and adaptive immune responses but also plays an important role in inflammation, antiviral response, and cell development. However, the exact role of IRF9 in osteoclasts has not been reported. To elucidate the role of IRF9 in osteoclast differentiation, we established the ovariectomized mouse model of postmenopausal osteoporosis and found that IRF9 expression was reduced in ovariectomized mice with overactive osteoclasts. Furthermore, knockdown of IRF9 expression enhanced osteoclast differentiation in vitro. Using RNA sequencing, we identified that the differentially expressed genes enriched by IRF9 knockdown were related to ferroptosis. We observed that IRF9 knockdown promoted osteoclast differentiation via decreased ferroptosis in vitro and further verified that IRF9 knockdown reduced ferroptosis by activating signal transducer and activator of transcription 3 (STAT3) to promote osteoclastogenesis. In conclusion, we identified an essential role of IRF9 in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism. |
| doi_str_mv | 10.1007/s10753-023-01896-1 |
| format | Article |
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Inhibiting osteoclast hyperactivity is a key aspect of osteoporosis prevention and treatment. Several studies have shown that interferon regulatory factor 9 (IRF9) not only regulates innate and adaptive immune responses but also plays an important role in inflammation, antiviral response, and cell development. However, the exact role of IRF9 in osteoclasts has not been reported. To elucidate the role of IRF9 in osteoclast differentiation, we established the ovariectomized mouse model of postmenopausal osteoporosis and found that IRF9 expression was reduced in ovariectomized mice with overactive osteoclasts. Furthermore, knockdown of IRF9 expression enhanced osteoclast differentiation in vitro. Using RNA sequencing, we identified that the differentially expressed genes enriched by IRF9 knockdown were related to ferroptosis. We observed that IRF9 knockdown promoted osteoclast differentiation via decreased ferroptosis in vitro and further verified that IRF9 knockdown reduced ferroptosis by activating signal transducer and activator of transcription 3 (STAT3) to promote osteoclastogenesis. In conclusion, we identified an essential role of IRF9 in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.</description><identifier>ISSN: 0360-3997</identifier><identifier>EISSN: 1573-2576</identifier><identifier>DOI: 10.1007/s10753-023-01896-1</identifier><identifier>PMID: 37804406</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Aged ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Bone Resorption - metabolism ; Cell Differentiation ; Chronic illnesses ; Ferroptosis ; Humans ; Hyperactivity ; Immune response ; Immunology ; Interferon regulatory factor ; Interferon-Stimulated Gene Factor 3, gamma Subunit - metabolism ; Internal Medicine ; Mice ; Osteoclastogenesis ; Osteoclasts ; Osteoclasts - metabolism ; Osteogenesis ; Osteoporosis ; Osteoporosis - metabolism ; Ovariectomy ; Pathology ; Pharmacology/Toxicology ; Post-menopause ; RANK Ligand - metabolism ; Rheumatology ; Signal Transduction ; Stat3 protein ; STAT3 Transcription Factor - metabolism</subject><ispartof>Inflammation, 2024-02, Vol.47 (1), p.99-113</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. 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Inhibiting osteoclast hyperactivity is a key aspect of osteoporosis prevention and treatment. Several studies have shown that interferon regulatory factor 9 (IRF9) not only regulates innate and adaptive immune responses but also plays an important role in inflammation, antiviral response, and cell development. However, the exact role of IRF9 in osteoclasts has not been reported. To elucidate the role of IRF9 in osteoclast differentiation, we established the ovariectomized mouse model of postmenopausal osteoporosis and found that IRF9 expression was reduced in ovariectomized mice with overactive osteoclasts. Furthermore, knockdown of IRF9 expression enhanced osteoclast differentiation in vitro. Using RNA sequencing, we identified that the differentially expressed genes enriched by IRF9 knockdown were related to ferroptosis. We observed that IRF9 knockdown promoted osteoclast differentiation via decreased ferroptosis in vitro and further verified that IRF9 knockdown reduced ferroptosis by activating signal transducer and activator of transcription 3 (STAT3) to promote osteoclastogenesis. In conclusion, we identified an essential role of IRF9 in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.</description><subject>Aged</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bone Resorption - metabolism</subject><subject>Cell Differentiation</subject><subject>Chronic illnesses</subject><subject>Ferroptosis</subject><subject>Humans</subject><subject>Hyperactivity</subject><subject>Immune response</subject><subject>Immunology</subject><subject>Interferon regulatory factor</subject><subject>Interferon-Stimulated Gene Factor 3, gamma Subunit - metabolism</subject><subject>Internal Medicine</subject><subject>Mice</subject><subject>Osteoclastogenesis</subject><subject>Osteoclasts</subject><subject>Osteoclasts - metabolism</subject><subject>Osteogenesis</subject><subject>Osteoporosis</subject><subject>Osteoporosis - metabolism</subject><subject>Ovariectomy</subject><subject>Pathology</subject><subject>Pharmacology/Toxicology</subject><subject>Post-menopause</subject><subject>RANK Ligand - metabolism</subject><subject>Rheumatology</subject><subject>Signal Transduction</subject><subject>Stat3 protein</subject><subject>STAT3 Transcription Factor - metabolism</subject><issn>0360-3997</issn><issn>1573-2576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kU1vEzEQhi0EakPKH-CALHHhsjC2469j1DZQqVJRG86W486irZL14tmt1H9fp2mpxIHDaA7zzDsfL2MfBXwVAPYbCbBaNSBrCOdNI96wmdBWNVJb85bNQBlolPf2mL0nugMA5506YsfKOlgswMwY3kzDUJCoyz3PLb-4Xnn-s-RdHpH4FY2Y0zbSyM-6tsWC_djFcc9uHvgZpoKR8JavsJQ8jJk64vdd5Dfr5VrxZRq7-yf6hL1r45bww3Oes1-r8_Xpj-by6vvF6fKyScrqsYmYrFMtYHTWOQQjFRqZokURwSvt29anJDRsdGUW1li0m3pq1FI5r52asy8H3aHkPxPSGHYdJdxuY495oiCdXUjtrNmjn_9B7_JU-rpdkF4YDRLqY-dMHqhUMlHBNgyl28XyEASEvQnhYEKobHgyIYja9OlZetrs8PZvy8vXK6AOANVS_xvL6-z_yD4CPc6RXQ</recordid><startdate>20240201</startdate><enddate>20240201</enddate><creator>Lan, Chao</creator><creator>Zhou, Xuan</creator><creator>Shen, Ximei</creator><creator>Lin, Youfen</creator><creator>Chen, Xiaoyuan</creator><creator>Lin, Jiebin</creator><creator>Zhang, Yongze</creator><creator>Zheng, Lifeng</creator><creator>Yan, Sunjie</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20240201</creationdate><title>Suppression of IRF9 Promotes Osteoclast Differentiation by Decreased Ferroptosis via STAT3 Activation</title><author>Lan, Chao ; 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Inhibiting osteoclast hyperactivity is a key aspect of osteoporosis prevention and treatment. Several studies have shown that interferon regulatory factor 9 (IRF9) not only regulates innate and adaptive immune responses but also plays an important role in inflammation, antiviral response, and cell development. However, the exact role of IRF9 in osteoclasts has not been reported. To elucidate the role of IRF9 in osteoclast differentiation, we established the ovariectomized mouse model of postmenopausal osteoporosis and found that IRF9 expression was reduced in ovariectomized mice with overactive osteoclasts. Furthermore, knockdown of IRF9 expression enhanced osteoclast differentiation in vitro. Using RNA sequencing, we identified that the differentially expressed genes enriched by IRF9 knockdown were related to ferroptosis. We observed that IRF9 knockdown promoted osteoclast differentiation via decreased ferroptosis in vitro and further verified that IRF9 knockdown reduced ferroptosis by activating signal transducer and activator of transcription 3 (STAT3) to promote osteoclastogenesis. In conclusion, we identified an essential role of IRF9 in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>37804406</pmid><doi>10.1007/s10753-023-01896-1</doi><tpages>15</tpages></addata></record> |
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| subjects | Aged Animals Biomedical and Life Sciences Biomedicine Bone Resorption - metabolism Cell Differentiation Chronic illnesses Ferroptosis Humans Hyperactivity Immune response Immunology Interferon regulatory factor Interferon-Stimulated Gene Factor 3, gamma Subunit - metabolism Internal Medicine Mice Osteoclastogenesis Osteoclasts Osteoclasts - metabolism Osteogenesis Osteoporosis Osteoporosis - metabolism Ovariectomy Pathology Pharmacology/Toxicology Post-menopause RANK Ligand - metabolism Rheumatology Signal Transduction Stat3 protein STAT3 Transcription Factor - metabolism |
| title | Suppression of IRF9 Promotes Osteoclast Differentiation by Decreased Ferroptosis via STAT3 Activation |
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