Osthole accelerates osteoporotic fracture healing by inducing the osteogenesis–angiogenesis coupling of BMSCs via the Wnt/β‐catenin pathway
Osthole, a natural coumarin derivative, has been shown to have multiple pharmacological activities. However, its effect on osteoporotic fracture has not yet been examined. This research was designed to explore the unknown role and potential mechanism of osthole on osteoporotic fracture healing. We f...
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| Veröffentlicht in: | Phytotherapy research 2024-08, Vol.38 (8), p.4022-4035 |
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| creator | Zheng, Sheng Hu, Guanyu Zheng, Jia Li, Yikai Li, Junhua |
| description | Osthole, a natural coumarin derivative, has been shown to have multiple pharmacological activities. However, its effect on osteoporotic fracture has not yet been examined. This research was designed to explore the unknown role and potential mechanism of osthole on osteoporotic fracture healing. We first evaluated the osteogenic and angiogenic abilities of osthole. Then angiogenesis‐related assays were conducted to investigate the relationship between osteogenesis and angiogenesis, and further explore its molecular mechanism. After that, we established osteoporotic fracture model in ovariectomy‐induced osteoporosis rats and treated the rats with osthole or placebo. Radiography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of osthole on osteoporotic fracture healing. In vitro research revealed that osthole promoted osteogenesis and up‐regulated the expression of angiogenic‐related markers. Further research found that osthole couldn't facilitate the angiogenesis of human umbilical vein endothelial cells in a direct manner, but it possessed the ability to induce the osteogenesis–angiogenesis coupling of bone marrow mesenchymal stem cells (BMSCs). Mechanistically, this was conducted through activating the Wnt/β‐catenin pathway. Subsequently, using ovariectomy‐induced osteoporosis tibia fracture rat model, we observed that osthole facilitated bone formation and CD31hiEMCNhi type H‐positive capillary formation. Sequential fluorescent labeling confirmed that osthole could effectively accelerate bone formation in the fractured region. The data above indicated that osthole could accelerate osteoporotic fracture healing by inducing the osteogenesis–angiogenesis coupling of BMSCs via the Wnt/β‐catenin pathway, which implied that osthole may be a potential drug for treating osteoporosis fracture. |
| doi_str_mv | 10.1002/ptr.8267 |
| format | Article |
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However, its effect on osteoporotic fracture has not yet been examined. This research was designed to explore the unknown role and potential mechanism of osthole on osteoporotic fracture healing. We first evaluated the osteogenic and angiogenic abilities of osthole. Then angiogenesis‐related assays were conducted to investigate the relationship between osteogenesis and angiogenesis, and further explore its molecular mechanism. After that, we established osteoporotic fracture model in ovariectomy‐induced osteoporosis rats and treated the rats with osthole or placebo. Radiography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of osthole on osteoporotic fracture healing. In vitro research revealed that osthole promoted osteogenesis and up‐regulated the expression of angiogenic‐related markers. Further research found that osthole couldn't facilitate the angiogenesis of human umbilical vein endothelial cells in a direct manner, but it possessed the ability to induce the osteogenesis–angiogenesis coupling of bone marrow mesenchymal stem cells (BMSCs). Mechanistically, this was conducted through activating the Wnt/β‐catenin pathway. Subsequently, using ovariectomy‐induced osteoporosis tibia fracture rat model, we observed that osthole facilitated bone formation and CD31hiEMCNhi type H‐positive capillary formation. Sequential fluorescent labeling confirmed that osthole could effectively accelerate bone formation in the fractured region. The data above indicated that osthole could accelerate osteoporotic fracture healing by inducing the osteogenesis–angiogenesis coupling of BMSCs via the Wnt/β‐catenin pathway, which implied that osthole may be a potential drug for treating osteoporosis fracture.</description><identifier>ISSN: 0951-418X</identifier><identifier>ISSN: 1099-1573</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.8267</identifier><identifier>PMID: 38873735</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Angiogenesis ; animal models ; Animals ; beta Catenin - metabolism ; bone formation ; bone fractures ; Bone growth ; Bone healing ; Bone marrow ; bone marrow mesenchymal stem cells ; Catenin ; Coumarin ; Coumarins - pharmacology ; Disease Models, Animal ; drugs ; Endothelial cells ; Female ; Fluorescence ; Fracture Healing - drug effects ; Fractures ; Healing ; Histology ; Human performance ; Human Umbilical Vein Endothelial Cells - drug effects ; Humans ; Labelling ; Mesenchymal stem cells ; Mesenchymal Stem Cells - drug effects ; Molecular modelling ; Neovascularization, Physiologic - drug effects ; Oophorectomy ; Osteogenesis ; Osteogenesis - drug effects ; osteogenesis–angiogenesis coupling ; Osteoporosis ; Osteoporosis - drug therapy ; osteoporotic fracture ; Osteoporotic Fractures - drug therapy ; osthole ; Ovariectomy ; phytotherapy ; placebos ; Radiography ; Rats ; Rats, Sprague-Dawley ; Stem cells ; Tibia ; Umbilical vein ; Wnt protein ; Wnt Signaling Pathway - drug effects ; Wnt/β‐catenin</subject><ispartof>Phytotherapy research, 2024-08, Vol.38 (8), p.4022-4035</ispartof><rights>2024 John Wiley & Sons Ltd.</rights><rights>2024 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3437-44f53125d4ff620afafc67b53c141097a641aac036c9053612feaf0ccb25b0573</cites><orcidid>0000-0001-6525-8721 ; 0000-0003-0766-6051</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%2Fptr.8267$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.8267$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38873735$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zheng, Sheng</creatorcontrib><creatorcontrib>Hu, Guanyu</creatorcontrib><creatorcontrib>Zheng, Jia</creatorcontrib><creatorcontrib>Li, Yikai</creatorcontrib><creatorcontrib>Li, Junhua</creatorcontrib><title>Osthole accelerates osteoporotic fracture healing by inducing the osteogenesis–angiogenesis coupling of BMSCs via the Wnt/β‐catenin pathway</title><title>Phytotherapy research</title><addtitle>Phytother Res</addtitle><description>Osthole, a natural coumarin derivative, has been shown to have multiple pharmacological activities. However, its effect on osteoporotic fracture has not yet been examined. This research was designed to explore the unknown role and potential mechanism of osthole on osteoporotic fracture healing. We first evaluated the osteogenic and angiogenic abilities of osthole. Then angiogenesis‐related assays were conducted to investigate the relationship between osteogenesis and angiogenesis, and further explore its molecular mechanism. After that, we established osteoporotic fracture model in ovariectomy‐induced osteoporosis rats and treated the rats with osthole or placebo. Radiography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of osthole on osteoporotic fracture healing. In vitro research revealed that osthole promoted osteogenesis and up‐regulated the expression of angiogenic‐related markers. Further research found that osthole couldn't facilitate the angiogenesis of human umbilical vein endothelial cells in a direct manner, but it possessed the ability to induce the osteogenesis–angiogenesis coupling of bone marrow mesenchymal stem cells (BMSCs). Mechanistically, this was conducted through activating the Wnt/β‐catenin pathway. Subsequently, using ovariectomy‐induced osteoporosis tibia fracture rat model, we observed that osthole facilitated bone formation and CD31hiEMCNhi type H‐positive capillary formation. Sequential fluorescent labeling confirmed that osthole could effectively accelerate bone formation in the fractured region. The data above indicated that osthole could accelerate osteoporotic fracture healing by inducing the osteogenesis–angiogenesis coupling of BMSCs via the Wnt/β‐catenin pathway, which implied that osthole may be a potential drug for treating osteoporosis fracture.</description><subject>Angiogenesis</subject><subject>animal models</subject><subject>Animals</subject><subject>beta Catenin - metabolism</subject><subject>bone formation</subject><subject>bone fractures</subject><subject>Bone growth</subject><subject>Bone healing</subject><subject>Bone marrow</subject><subject>bone marrow mesenchymal stem cells</subject><subject>Catenin</subject><subject>Coumarin</subject><subject>Coumarins - pharmacology</subject><subject>Disease Models, Animal</subject><subject>drugs</subject><subject>Endothelial cells</subject><subject>Female</subject><subject>Fluorescence</subject><subject>Fracture Healing - drug effects</subject><subject>Fractures</subject><subject>Healing</subject><subject>Histology</subject><subject>Human performance</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Humans</subject><subject>Labelling</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - drug effects</subject><subject>Molecular modelling</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Oophorectomy</subject><subject>Osteogenesis</subject><subject>Osteogenesis - drug effects</subject><subject>osteogenesis–angiogenesis coupling</subject><subject>Osteoporosis</subject><subject>Osteoporosis - drug therapy</subject><subject>osteoporotic fracture</subject><subject>Osteoporotic Fractures - drug therapy</subject><subject>osthole</subject><subject>Ovariectomy</subject><subject>phytotherapy</subject><subject>placebos</subject><subject>Radiography</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Stem cells</subject><subject>Tibia</subject><subject>Umbilical vein</subject><subject>Wnt protein</subject><subject>Wnt Signaling Pathway - drug effects</subject><subject>Wnt/β‐catenin</subject><issn>0951-418X</issn><issn>1099-1573</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd1qFDEYhkNR2rUWegUS8MSTafM7mRzq4h9UKlrRsyGTTXZTZpMxyVj2rJdQ6J30QryIXonZ3f6AIB4lged7wve-ABxidIQRIsdDjkcNqcUOmGAkZYW5oE_ABEmOK4abH3vgWUrnCCFJENsFe7RpBBWUT8DVacqL0BuotDa9iSqbBEPKJgwhhuw0tFHpPEYDF0b1zs9ht4LOz0a9vueF2dJz401y6fbyWvm5u39CHcZhMxQsfPPp6zTBX05tpr77fPz75vbySpcvvfNwUHlxoVbPwVOr-mQO7s598O3d27Pph-rk9P3H6euTSlNGRcWY5RQTPmPW1gQpq6yuRcepxqxEIFTNsFIa0VpLxGmNiTXKIq07wjtU4tkHr7beIYafo0m5XbpUIuiVN2FMLcWcCkYob_6PoroRvJECF_TlX-h5GKMvixRKEiKZRPRRqGNIKRrbDtEtVVy1GLXrQttSaLsutKAv7oRjtzSzB_C-wQJUW-DC9Wb1T1H7-ezLRvgHIwuubA</recordid><startdate>202408</startdate><enddate>202408</enddate><creator>Zheng, Sheng</creator><creator>Hu, Guanyu</creator><creator>Zheng, Jia</creator><creator>Li, Yikai</creator><creator>Li, Junhua</creator><general>John Wiley & Sons, Ltd</general><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>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0001-6525-8721</orcidid><orcidid>https://orcid.org/0000-0003-0766-6051</orcidid></search><sort><creationdate>202408</creationdate><title>Osthole accelerates osteoporotic fracture healing by inducing the osteogenesis–angiogenesis coupling of BMSCs via the Wnt/β‐catenin pathway</title><author>Zheng, Sheng ; Hu, Guanyu ; Zheng, Jia ; Li, Yikai ; Li, Junhua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3437-44f53125d4ff620afafc67b53c141097a641aac036c9053612feaf0ccb25b0573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Angiogenesis</topic><topic>animal models</topic><topic>Animals</topic><topic>beta Catenin - metabolism</topic><topic>bone formation</topic><topic>bone fractures</topic><topic>Bone growth</topic><topic>Bone healing</topic><topic>Bone marrow</topic><topic>bone marrow mesenchymal stem cells</topic><topic>Catenin</topic><topic>Coumarin</topic><topic>Coumarins - pharmacology</topic><topic>Disease Models, Animal</topic><topic>drugs</topic><topic>Endothelial cells</topic><topic>Female</topic><topic>Fluorescence</topic><topic>Fracture Healing - drug effects</topic><topic>Fractures</topic><topic>Healing</topic><topic>Histology</topic><topic>Human performance</topic><topic>Human Umbilical Vein Endothelial Cells - drug effects</topic><topic>Humans</topic><topic>Labelling</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stem Cells - drug effects</topic><topic>Molecular modelling</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Oophorectomy</topic><topic>Osteogenesis</topic><topic>Osteogenesis - drug effects</topic><topic>osteogenesis–angiogenesis coupling</topic><topic>Osteoporosis</topic><topic>Osteoporosis - drug therapy</topic><topic>osteoporotic fracture</topic><topic>Osteoporotic Fractures - drug therapy</topic><topic>osthole</topic><topic>Ovariectomy</topic><topic>phytotherapy</topic><topic>placebos</topic><topic>Radiography</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Stem cells</topic><topic>Tibia</topic><topic>Umbilical vein</topic><topic>Wnt protein</topic><topic>Wnt Signaling Pathway - drug effects</topic><topic>Wnt/β‐catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zheng, Sheng</creatorcontrib><creatorcontrib>Hu, Guanyu</creatorcontrib><creatorcontrib>Zheng, Jia</creatorcontrib><creatorcontrib>Li, Yikai</creatorcontrib><creatorcontrib>Li, Junhua</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</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><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Phytotherapy research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zheng, Sheng</au><au>Hu, Guanyu</au><au>Zheng, Jia</au><au>Li, Yikai</au><au>Li, Junhua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Osthole accelerates osteoporotic fracture healing by inducing the osteogenesis–angiogenesis coupling of BMSCs via the Wnt/β‐catenin pathway</atitle><jtitle>Phytotherapy research</jtitle><addtitle>Phytother Res</addtitle><date>2024-08</date><risdate>2024</risdate><volume>38</volume><issue>8</issue><spage>4022</spage><epage>4035</epage><pages>4022-4035</pages><issn>0951-418X</issn><issn>1099-1573</issn><eissn>1099-1573</eissn><abstract>Osthole, a natural coumarin derivative, has been shown to have multiple pharmacological activities. However, its effect on osteoporotic fracture has not yet been examined. This research was designed to explore the unknown role and potential mechanism of osthole on osteoporotic fracture healing. We first evaluated the osteogenic and angiogenic abilities of osthole. Then angiogenesis‐related assays were conducted to investigate the relationship between osteogenesis and angiogenesis, and further explore its molecular mechanism. After that, we established osteoporotic fracture model in ovariectomy‐induced osteoporosis rats and treated the rats with osthole or placebo. Radiography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of osthole on osteoporotic fracture healing. In vitro research revealed that osthole promoted osteogenesis and up‐regulated the expression of angiogenic‐related markers. Further research found that osthole couldn't facilitate the angiogenesis of human umbilical vein endothelial cells in a direct manner, but it possessed the ability to induce the osteogenesis–angiogenesis coupling of bone marrow mesenchymal stem cells (BMSCs). Mechanistically, this was conducted through activating the Wnt/β‐catenin pathway. Subsequently, using ovariectomy‐induced osteoporosis tibia fracture rat model, we observed that osthole facilitated bone formation and CD31hiEMCNhi type H‐positive capillary formation. Sequential fluorescent labeling confirmed that osthole could effectively accelerate bone formation in the fractured region. The data above indicated that osthole could accelerate osteoporotic fracture healing by inducing the osteogenesis–angiogenesis coupling of BMSCs via the Wnt/β‐catenin pathway, which implied that osthole may be a potential drug for treating osteoporosis fracture.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>38873735</pmid><doi>10.1002/ptr.8267</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-6525-8721</orcidid><orcidid>https://orcid.org/0000-0003-0766-6051</orcidid></addata></record> |
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| subjects | Angiogenesis animal models Animals beta Catenin - metabolism bone formation bone fractures Bone growth Bone healing Bone marrow bone marrow mesenchymal stem cells Catenin Coumarin Coumarins - pharmacology Disease Models, Animal drugs Endothelial cells Female Fluorescence Fracture Healing - drug effects Fractures Healing Histology Human performance Human Umbilical Vein Endothelial Cells - drug effects Humans Labelling Mesenchymal stem cells Mesenchymal Stem Cells - drug effects Molecular modelling Neovascularization, Physiologic - drug effects Oophorectomy Osteogenesis Osteogenesis - drug effects osteogenesis–angiogenesis coupling Osteoporosis Osteoporosis - drug therapy osteoporotic fracture Osteoporotic Fractures - drug therapy osthole Ovariectomy phytotherapy placebos Radiography Rats Rats, Sprague-Dawley Stem cells Tibia Umbilical vein Wnt protein Wnt Signaling Pathway - drug effects Wnt/β‐catenin |
| title | Osthole accelerates osteoporotic fracture healing by inducing the osteogenesis–angiogenesis coupling of BMSCs via the Wnt/β‐catenin pathway |
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