Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways
In this study, we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy (OVX)-induced osteoporosis model mice. Puerarin-treated OVX mice exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAcP)-positive osteoclasts, and l...
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| Veröffentlicht in: | Aging (Albany, NY.) NY.), 2020-11, Vol.12 (21), p.21706-21729 |
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| creator | Xiao, Long Zhong, Mengdan Huang, Yu Zhu, Jie Tang, Wenkai Li, Danyong Shi, Jiandong Lu, Aiqing Yang, Huilin Geng, Dechun Li, Hong Wang, Zhirong |
| description | In this study, we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy (OVX)-induced osteoporosis model mice. Puerarin-treated OVX mice exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAcP)-positive osteoclasts, and levels of lower reactive oxygen species (ROS) within bone tissues than vehicle-treated OVX mice. Puerarin suppressed
osteoclast differentiation, hydroxyapatite resorption activity, and expression of osteoclastogenesis-related genes, such as NFATc1, MMP9, CTSK, Acp5 and c-Fos, in RANKL-induced bone marrow macrophages (BMMs) and RAW264.7 cells. It also reduced intracellular ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 (NOX1) and increasing expression of antioxidant enzymes such as heme oxygenase-1 (HO-1). Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK and NF-κB signaling pathways in RANKL-induced RAW264.7 cells, and these effects were partially reversed by HO-1 silencing or TRAF6 overexpression. These findings suggest puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition of the TRAF6/ROS-dependent MAPK/NF-κB signaling pathway. |
| doi_str_mv | 10.18632/aging.103976 |
| format | Article |
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osteoclast differentiation, hydroxyapatite resorption activity, and expression of osteoclastogenesis-related genes, such as NFATc1, MMP9, CTSK, Acp5 and c-Fos, in RANKL-induced bone marrow macrophages (BMMs) and RAW264.7 cells. It also reduced intracellular ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 (NOX1) and increasing expression of antioxidant enzymes such as heme oxygenase-1 (HO-1). Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK and NF-κB signaling pathways in RANKL-induced RAW264.7 cells, and these effects were partially reversed by HO-1 silencing or TRAF6 overexpression. These findings suggest puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition of the TRAF6/ROS-dependent MAPK/NF-κB signaling pathway.</description><identifier>ISSN: 1945-4589</identifier><identifier>EISSN: 1945-4589</identifier><identifier>DOI: 10.18632/aging.103976</identifier><identifier>PMID: 33176281</identifier><language>eng</language><publisher>United States: Impact Journals</publisher><subject>Animals ; Female ; Humans ; Isoflavones - pharmacology ; MAP Kinase Signaling System - drug effects ; Mice ; Mice, Inbred C57BL ; NF-kappa B - metabolism ; Osteoclasts - drug effects ; Osteoclasts - metabolism ; Osteogenesis - drug effects ; Osteoporosis, Postmenopausal - metabolism ; Osteoporosis, Postmenopausal - pathology ; Ovariectomy ; RAW 264.7 Cells ; Reactive Oxygen Species ; Research Paper ; Signal Transduction - drug effects ; TNF Receptor-Associated Factor 6 - metabolism</subject><ispartof>Aging (Albany, NY.), 2020-11, Vol.12 (21), p.21706-21729</ispartof><rights>Copyright: © 2020 Xiao et al.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-10317007f541a092a5b5c0d1d299bbf23272240e5d5a4e145f9e11d1f5a557ec3</citedby><cites>FETCH-LOGICAL-c387t-10317007f541a092a5b5c0d1d299bbf23272240e5d5a4e145f9e11d1f5a557ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695364/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695364/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33176281$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiao, Long</creatorcontrib><creatorcontrib>Zhong, Mengdan</creatorcontrib><creatorcontrib>Huang, Yu</creatorcontrib><creatorcontrib>Zhu, Jie</creatorcontrib><creatorcontrib>Tang, Wenkai</creatorcontrib><creatorcontrib>Li, Danyong</creatorcontrib><creatorcontrib>Shi, Jiandong</creatorcontrib><creatorcontrib>Lu, Aiqing</creatorcontrib><creatorcontrib>Yang, Huilin</creatorcontrib><creatorcontrib>Geng, Dechun</creatorcontrib><creatorcontrib>Li, Hong</creatorcontrib><creatorcontrib>Wang, Zhirong</creatorcontrib><title>Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways</title><title>Aging (Albany, NY.)</title><addtitle>Aging (Albany NY)</addtitle><description>In this study, we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy (OVX)-induced osteoporosis model mice. Puerarin-treated OVX mice exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAcP)-positive osteoclasts, and levels of lower reactive oxygen species (ROS) within bone tissues than vehicle-treated OVX mice. Puerarin suppressed
osteoclast differentiation, hydroxyapatite resorption activity, and expression of osteoclastogenesis-related genes, such as NFATc1, MMP9, CTSK, Acp5 and c-Fos, in RANKL-induced bone marrow macrophages (BMMs) and RAW264.7 cells. It also reduced intracellular ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 (NOX1) and increasing expression of antioxidant enzymes such as heme oxygenase-1 (HO-1). Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK and NF-κB signaling pathways in RANKL-induced RAW264.7 cells, and these effects were partially reversed by HO-1 silencing or TRAF6 overexpression. These findings suggest puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition of the TRAF6/ROS-dependent MAPK/NF-κB signaling pathway.</description><subject>Animals</subject><subject>Female</subject><subject>Humans</subject><subject>Isoflavones - pharmacology</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>NF-kappa B - metabolism</subject><subject>Osteoclasts - drug effects</subject><subject>Osteoclasts - metabolism</subject><subject>Osteogenesis - drug effects</subject><subject>Osteoporosis, Postmenopausal - metabolism</subject><subject>Osteoporosis, Postmenopausal - pathology</subject><subject>Ovariectomy</subject><subject>RAW 264.7 Cells</subject><subject>Reactive Oxygen Species</subject><subject>Research Paper</subject><subject>Signal Transduction - drug effects</subject><subject>TNF Receptor-Associated Factor 6 - metabolism</subject><issn>1945-4589</issn><issn>1945-4589</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc9u1DAQxiMEoqVw5Ip85JKuHf9JckFaKhYQhValnC3HnmSNEjvYzqJ9It6Bh-CZcLulKqcZab75zaf5iuIlwaekEbRaqcG64ZRg2tbiUXFMWsZLxpv28YP-qHgW43eMBedMPC2OKCW1qBpyXPy6XCCoYB1S4wg7qxJE5GMCP_vgo40oj9IWkN9lFejkp31pnVk0GDRZDajbo7jMc4AYs5HDrh5VTH4ABzeETM2Ure1sst4h36Prq_VGrK4uvpYGZnAGXEKf15efVl825Z_fb1G0g1PjDW5WaftT7ePz4kmvxggv7upJ8W3z7vrsQ3l-8f7j2fq81LSpU5nfQGqM654zonBbKd5xjQ0xVdt2XV_Rqq4qhoEbrhgQxvsWCDGk54rzGjQ9Kd4cuPPSTWB0dhbUKOdgJxX20isr_584u5WD38latJwKlgGv7wDB_1ggJjnZqGEclQO_RFkxgXFDcsnS8iDV-dMxQH9_hmB5G668DVcews36Vw-93av_pUn_AhkBphw</recordid><startdate>20201107</startdate><enddate>20201107</enddate><creator>Xiao, Long</creator><creator>Zhong, Mengdan</creator><creator>Huang, Yu</creator><creator>Zhu, Jie</creator><creator>Tang, Wenkai</creator><creator>Li, Danyong</creator><creator>Shi, Jiandong</creator><creator>Lu, Aiqing</creator><creator>Yang, Huilin</creator><creator>Geng, Dechun</creator><creator>Li, Hong</creator><creator>Wang, Zhirong</creator><general>Impact Journals</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20201107</creationdate><title>Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways</title><author>Xiao, Long ; Zhong, Mengdan ; Huang, Yu ; Zhu, Jie ; Tang, Wenkai ; Li, Danyong ; Shi, Jiandong ; Lu, Aiqing ; Yang, Huilin ; Geng, Dechun ; Li, Hong ; Wang, Zhirong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-10317007f541a092a5b5c0d1d299bbf23272240e5d5a4e145f9e11d1f5a557ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Female</topic><topic>Humans</topic><topic>Isoflavones - pharmacology</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>NF-kappa B - metabolism</topic><topic>Osteoclasts - drug effects</topic><topic>Osteoclasts - metabolism</topic><topic>Osteogenesis - drug effects</topic><topic>Osteoporosis, Postmenopausal - metabolism</topic><topic>Osteoporosis, Postmenopausal - pathology</topic><topic>Ovariectomy</topic><topic>RAW 264.7 Cells</topic><topic>Reactive Oxygen Species</topic><topic>Research Paper</topic><topic>Signal Transduction - drug effects</topic><topic>TNF Receptor-Associated Factor 6 - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>Xiao, Long</creatorcontrib><creatorcontrib>Zhong, Mengdan</creatorcontrib><creatorcontrib>Huang, Yu</creatorcontrib><creatorcontrib>Zhu, Jie</creatorcontrib><creatorcontrib>Tang, Wenkai</creatorcontrib><creatorcontrib>Li, Danyong</creatorcontrib><creatorcontrib>Shi, Jiandong</creatorcontrib><creatorcontrib>Lu, Aiqing</creatorcontrib><creatorcontrib>Yang, Huilin</creatorcontrib><creatorcontrib>Geng, Dechun</creatorcontrib><creatorcontrib>Li, Hong</creatorcontrib><creatorcontrib>Wang, Zhirong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging (Albany, NY.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiao, Long</au><au>Zhong, Mengdan</au><au>Huang, Yu</au><au>Zhu, Jie</au><au>Tang, Wenkai</au><au>Li, Danyong</au><au>Shi, Jiandong</au><au>Lu, Aiqing</au><au>Yang, Huilin</au><au>Geng, Dechun</au><au>Li, Hong</au><au>Wang, Zhirong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways</atitle><jtitle>Aging (Albany, NY.)</jtitle><addtitle>Aging (Albany NY)</addtitle><date>2020-11-07</date><risdate>2020</risdate><volume>12</volume><issue>21</issue><spage>21706</spage><epage>21729</epage><pages>21706-21729</pages><issn>1945-4589</issn><eissn>1945-4589</eissn><abstract>In this study, we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy (OVX)-induced osteoporosis model mice. Puerarin-treated OVX mice exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAcP)-positive osteoclasts, and levels of lower reactive oxygen species (ROS) within bone tissues than vehicle-treated OVX mice. Puerarin suppressed
osteoclast differentiation, hydroxyapatite resorption activity, and expression of osteoclastogenesis-related genes, such as NFATc1, MMP9, CTSK, Acp5 and c-Fos, in RANKL-induced bone marrow macrophages (BMMs) and RAW264.7 cells. It also reduced intracellular ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 (NOX1) and increasing expression of antioxidant enzymes such as heme oxygenase-1 (HO-1). Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK and NF-κB signaling pathways in RANKL-induced RAW264.7 cells, and these effects were partially reversed by HO-1 silencing or TRAF6 overexpression. These findings suggest puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition of the TRAF6/ROS-dependent MAPK/NF-κB signaling pathway.</abstract><cop>United States</cop><pub>Impact Journals</pub><pmid>33176281</pmid><doi>10.18632/aging.103976</doi><tpages>24</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Female Humans Isoflavones - pharmacology MAP Kinase Signaling System - drug effects Mice Mice, Inbred C57BL NF-kappa B - metabolism Osteoclasts - drug effects Osteoclasts - metabolism Osteogenesis - drug effects Osteoporosis, Postmenopausal - metabolism Osteoporosis, Postmenopausal - pathology Ovariectomy RAW 264.7 Cells Reactive Oxygen Species Research Paper Signal Transduction - drug effects TNF Receptor-Associated Factor 6 - metabolism |
| title | Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways |
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