Anti‐osteoporosis activity of Sanguinarine in preosteoblast MC3T3‐E1 cells and an ovariectomized rat model
Sanguinarine, a benzophenanthridine alkaloid, has been previously demonstrated to exert antimicrobial, anti‐inflammatory, and anti‐tumor activities. A previous study has identified Sanguinarine as a potential drug candidate for osteoporosis treatment by computational bioinformatics analysis. This st...
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| Veröffentlicht in: | Journal of cellular physiology 2018-06, Vol.233 (6), p.4626-4633 |
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| description | Sanguinarine, a benzophenanthridine alkaloid, has been previously demonstrated to exert antimicrobial, anti‐inflammatory, and anti‐tumor activities. A previous study has identified Sanguinarine as a potential drug candidate for osteoporosis treatment by computational bioinformatics analysis. This study further evaluated the effects of Sanguinarine on the differentiation of murine preosteoblast MC3T3‐E1 cells and its anti‐osteoporosis activity in an ovarietomized rat model. Sanguinarine treatment (0.25, 0.5, 1, and 2 µm) of MC3T3‐E1 cells significantly increased alkaline phosphatase (ALP) activity and the phoshporalyation of AMP‐activated protein kinase α subunit (AMPKα), but did not affect cell proliferation. The induction effects of Sanguinarine treatment (2 µm) on ALP activity, AMPKα phosphorylation, Smad1 phosphorylation, and the expression of three osteoblast differentiation‐regulators (bone morphogenetic protein 2 [BMP2], osterix [OSX], and osteoprotegerin [OPG]) were partially reversed by Compound C treatment. More importantly, Sanguinarine treatment promoted bone tissue growth in an ovariectomized (OVX) osteoporosis rat model as evaluated by histological examination, micro‐CT analysis, and serum parameter detection. In conclusion, these results indicate that Sanguinarine induces the differentiation of MC3T3‐E1 cells through the activation of the AMPK/Smad1 signaling pathway. Sanguinarine can stimulate bone growth in vivo and may be an effective drug for osteoporosis treatment.
Sanguinarine induces MC3T3‐E1 cell differentiation through the AMPK/Smad1 signaling pathway. Sanguinarine treatment promoted bone tissue growth in a rat model. |
| doi_str_mv | 10.1002/jcp.26187 |
| format | Article |
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Sanguinarine induces MC3T3‐E1 cell differentiation through the AMPK/Smad1 signaling pathway. Sanguinarine treatment promoted bone tissue growth in a rat model.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.26187</identifier><identifier>PMID: 28926099</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>3T3 Cells ; Alkaline phosphatase ; AMP ; AMP-Activated Protein Kinases - metabolism ; AMPKα ; Animals ; Benzophenanthridines - pharmacology ; Biocompatibility ; Bioinformatics ; Biomedical materials ; Bone Density - drug effects ; Bone Density Conservation Agents - pharmacology ; Bone growth ; Bone morphogenetic protein 2 ; Bone Remodeling - drug effects ; Cell Differentiation - drug effects ; Cell proliferation ; Computer applications ; Differentiation ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Humans ; Inflammation ; Isoquinolines - pharmacology ; Kinases ; Mice ; Osteoblastogenesis ; Osteoblasts - drug effects ; Osteoblasts - metabolism ; Osteoblasts - pathology ; Osteogenesis - drug effects ; Osteoporosis ; Osteoporosis, Postmenopausal - drug therapy ; Osteoporosis, Postmenopausal - metabolism ; Osteoporosis, Postmenopausal - pathology ; Osteoporosis, Postmenopausal - physiopathology ; osteoportosis ; Osteoprotegerin ; Ovariectomy ; Phosphorylation ; Protein kinase ; Rats, Sprague-Dawley ; Regulators ; Rodents ; Sanguinarine ; Signal transduction ; Signal Transduction - drug effects ; Signaling ; Smad1 Protein - metabolism</subject><ispartof>Journal of cellular physiology, 2018-06, Vol.233 (6), p.4626-4633</ispartof><rights>2017 Wiley Periodicals, Inc.</rights><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3537-dacd9c46dd73ffa1f22edac569cdfb5bc4db220019f9d25bf7c7c26f6a8193c03</citedby><cites>FETCH-LOGICAL-c3537-dacd9c46dd73ffa1f22edac569cdfb5bc4db220019f9d25bf7c7c26f6a8193c03</cites><orcidid>0000-0003-0482-0164</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.26187$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.26187$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27926,27927,45576,45577</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28926099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Fuzhan</creatorcontrib><creatorcontrib>Xie, Jile</creatorcontrib><creatorcontrib>Wang, Genlin</creatorcontrib><creatorcontrib>Zhang, Ge</creatorcontrib><creatorcontrib>Yang, Huilin</creatorcontrib><title>Anti‐osteoporosis activity of Sanguinarine in preosteoblast MC3T3‐E1 cells and an ovariectomized rat model</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>Sanguinarine, a benzophenanthridine alkaloid, has been previously demonstrated to exert antimicrobial, anti‐inflammatory, and anti‐tumor activities. A previous study has identified Sanguinarine as a potential drug candidate for osteoporosis treatment by computational bioinformatics analysis. This study further evaluated the effects of Sanguinarine on the differentiation of murine preosteoblast MC3T3‐E1 cells and its anti‐osteoporosis activity in an ovarietomized rat model. Sanguinarine treatment (0.25, 0.5, 1, and 2 µm) of MC3T3‐E1 cells significantly increased alkaline phosphatase (ALP) activity and the phoshporalyation of AMP‐activated protein kinase α subunit (AMPKα), but did not affect cell proliferation. The induction effects of Sanguinarine treatment (2 µm) on ALP activity, AMPKα phosphorylation, Smad1 phosphorylation, and the expression of three osteoblast differentiation‐regulators (bone morphogenetic protein 2 [BMP2], osterix [OSX], and osteoprotegerin [OPG]) were partially reversed by Compound C treatment. More importantly, Sanguinarine treatment promoted bone tissue growth in an ovariectomized (OVX) osteoporosis rat model as evaluated by histological examination, micro‐CT analysis, and serum parameter detection. In conclusion, these results indicate that Sanguinarine induces the differentiation of MC3T3‐E1 cells through the activation of the AMPK/Smad1 signaling pathway. Sanguinarine can stimulate bone growth in vivo and may be an effective drug for osteoporosis treatment.
Sanguinarine induces MC3T3‐E1 cell differentiation through the AMPK/Smad1 signaling pathway. Sanguinarine treatment promoted bone tissue growth in a rat model.</description><subject>3T3 Cells</subject><subject>Alkaline phosphatase</subject><subject>AMP</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>AMPKα</subject><subject>Animals</subject><subject>Benzophenanthridines - pharmacology</subject><subject>Biocompatibility</subject><subject>Bioinformatics</subject><subject>Biomedical materials</subject><subject>Bone Density - drug effects</subject><subject>Bone Density Conservation Agents - pharmacology</subject><subject>Bone growth</subject><subject>Bone morphogenetic protein 2</subject><subject>Bone Remodeling - drug effects</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell proliferation</subject><subject>Computer applications</subject><subject>Differentiation</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Isoquinolines - pharmacology</subject><subject>Kinases</subject><subject>Mice</subject><subject>Osteoblastogenesis</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - metabolism</subject><subject>Osteoblasts - pathology</subject><subject>Osteogenesis - drug effects</subject><subject>Osteoporosis</subject><subject>Osteoporosis, Postmenopausal - drug therapy</subject><subject>Osteoporosis, Postmenopausal - metabolism</subject><subject>Osteoporosis, Postmenopausal - pathology</subject><subject>Osteoporosis, Postmenopausal - physiopathology</subject><subject>osteoportosis</subject><subject>Osteoprotegerin</subject><subject>Ovariectomy</subject><subject>Phosphorylation</subject><subject>Protein kinase</subject><subject>Rats, Sprague-Dawley</subject><subject>Regulators</subject><subject>Rodents</subject><subject>Sanguinarine</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling</subject><subject>Smad1 Protein - metabolism</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1O3DAUha0K1BmmXfAClSU2ZRHwTxLHy9GIUhAIpNK15fgHeZTYwU6opiseoc_YJ6mHgS6QWFhX9v3O8dU9ABxidIIRIqdrNZyQGjfsA5hjxFlR1hXZA_PcwwWvSjwDBymtEUKcU_oRzEjDSZ0vc-CXfnR_n_6ENJowhBiSS1Cq0T26cQODhT-kv5-cl9F5A52HQzTPbNvJNMLrFb2jWX6GoTJdl6Ve5wPDYxYYNYbe_TYaRjnCPmjTfQL7VnbJfH6pC_Dz29nd6ntxdXN-sVpeFYpWlBVaKs1VWWvNqLUSW0JMfqtqrrRtq1aVuiUEIcwt16RqLVNMkdrWssGcKkQX4OvOd4jhYTJpFL1L2wmlN2FKAvMSVZyxkmT06A26DlP0eTqRf2hIwypUZup4R6m8ohSNFUN0vYwbgZHYhiByCOI5hMx-eXGc2t7o_-Tr1jNwugN-uc5s3ncSl6vbneU_HjmUDQ</recordid><startdate>201806</startdate><enddate>201806</enddate><creator>Zhang, Fuzhan</creator><creator>Xie, Jile</creator><creator>Wang, Genlin</creator><creator>Zhang, Ge</creator><creator>Yang, Huilin</creator><general>Wiley Subscription Services, Inc</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>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0482-0164</orcidid></search><sort><creationdate>201806</creationdate><title>Anti‐osteoporosis activity of Sanguinarine in preosteoblast MC3T3‐E1 cells and an ovariectomized rat model</title><author>Zhang, Fuzhan ; Xie, Jile ; Wang, Genlin ; Zhang, Ge ; Yang, Huilin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3537-dacd9c46dd73ffa1f22edac569cdfb5bc4db220019f9d25bf7c7c26f6a8193c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>3T3 Cells</topic><topic>Alkaline phosphatase</topic><topic>AMP</topic><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>AMPKα</topic><topic>Animals</topic><topic>Benzophenanthridines - pharmacology</topic><topic>Biocompatibility</topic><topic>Bioinformatics</topic><topic>Biomedical materials</topic><topic>Bone Density - drug effects</topic><topic>Bone Density Conservation Agents - pharmacology</topic><topic>Bone growth</topic><topic>Bone morphogenetic protein 2</topic><topic>Bone Remodeling - drug effects</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell proliferation</topic><topic>Computer applications</topic><topic>Differentiation</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Isoquinolines - pharmacology</topic><topic>Kinases</topic><topic>Mice</topic><topic>Osteoblastogenesis</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - metabolism</topic><topic>Osteoblasts - pathology</topic><topic>Osteogenesis - drug effects</topic><topic>Osteoporosis</topic><topic>Osteoporosis, Postmenopausal - drug therapy</topic><topic>Osteoporosis, Postmenopausal - metabolism</topic><topic>Osteoporosis, Postmenopausal - pathology</topic><topic>Osteoporosis, Postmenopausal - physiopathology</topic><topic>osteoportosis</topic><topic>Osteoprotegerin</topic><topic>Ovariectomy</topic><topic>Phosphorylation</topic><topic>Protein kinase</topic><topic>Rats, Sprague-Dawley</topic><topic>Regulators</topic><topic>Rodents</topic><topic>Sanguinarine</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signaling</topic><topic>Smad1 Protein - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Fuzhan</creatorcontrib><creatorcontrib>Xie, Jile</creatorcontrib><creatorcontrib>Wang, Genlin</creatorcontrib><creatorcontrib>Zhang, Ge</creatorcontrib><creatorcontrib>Yang, Huilin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Fuzhan</au><au>Xie, Jile</au><au>Wang, Genlin</au><au>Zhang, Ge</au><au>Yang, Huilin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti‐osteoporosis activity of Sanguinarine in preosteoblast MC3T3‐E1 cells and an ovariectomized rat model</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2018-06</date><risdate>2018</risdate><volume>233</volume><issue>6</issue><spage>4626</spage><epage>4633</epage><pages>4626-4633</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>Sanguinarine, a benzophenanthridine alkaloid, has been previously demonstrated to exert antimicrobial, anti‐inflammatory, and anti‐tumor activities. A previous study has identified Sanguinarine as a potential drug candidate for osteoporosis treatment by computational bioinformatics analysis. This study further evaluated the effects of Sanguinarine on the differentiation of murine preosteoblast MC3T3‐E1 cells and its anti‐osteoporosis activity in an ovarietomized rat model. Sanguinarine treatment (0.25, 0.5, 1, and 2 µm) of MC3T3‐E1 cells significantly increased alkaline phosphatase (ALP) activity and the phoshporalyation of AMP‐activated protein kinase α subunit (AMPKα), but did not affect cell proliferation. The induction effects of Sanguinarine treatment (2 µm) on ALP activity, AMPKα phosphorylation, Smad1 phosphorylation, and the expression of three osteoblast differentiation‐regulators (bone morphogenetic protein 2 [BMP2], osterix [OSX], and osteoprotegerin [OPG]) were partially reversed by Compound C treatment. More importantly, Sanguinarine treatment promoted bone tissue growth in an ovariectomized (OVX) osteoporosis rat model as evaluated by histological examination, micro‐CT analysis, and serum parameter detection. In conclusion, these results indicate that Sanguinarine induces the differentiation of MC3T3‐E1 cells through the activation of the AMPK/Smad1 signaling pathway. Sanguinarine can stimulate bone growth in vivo and may be an effective drug for osteoporosis treatment.
Sanguinarine induces MC3T3‐E1 cell differentiation through the AMPK/Smad1 signaling pathway. Sanguinarine treatment promoted bone tissue growth in a rat model.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28926099</pmid><doi>10.1002/jcp.26187</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0482-0164</orcidid></addata></record> |
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| subjects | 3T3 Cells Alkaline phosphatase AMP AMP-Activated Protein Kinases - metabolism AMPKα Animals Benzophenanthridines - pharmacology Biocompatibility Bioinformatics Biomedical materials Bone Density - drug effects Bone Density Conservation Agents - pharmacology Bone growth Bone morphogenetic protein 2 Bone Remodeling - drug effects Cell Differentiation - drug effects Cell proliferation Computer applications Differentiation Disease Models, Animal Dose-Response Relationship, Drug Female Humans Inflammation Isoquinolines - pharmacology Kinases Mice Osteoblastogenesis Osteoblasts - drug effects Osteoblasts - metabolism Osteoblasts - pathology Osteogenesis - drug effects Osteoporosis Osteoporosis, Postmenopausal - drug therapy Osteoporosis, Postmenopausal - metabolism Osteoporosis, Postmenopausal - pathology Osteoporosis, Postmenopausal - physiopathology osteoportosis Osteoprotegerin Ovariectomy Phosphorylation Protein kinase Rats, Sprague-Dawley Regulators Rodents Sanguinarine Signal transduction Signal Transduction - drug effects Signaling Smad1 Protein - metabolism |
| title | Anti‐osteoporosis activity of Sanguinarine in preosteoblast MC3T3‐E1 cells and an ovariectomized rat model |
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