Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts
ABSTRACTBone fracture healing is a complex, dynamic process that involves various cell types, with osteoclasts and osteoblasts playing indispensable roles. In this study, we found that psoralen, the main active ingredient in Psoralea corylifolia L. fruit extract, enhanced bone fracture healing throu...
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| Veröffentlicht in: | The FASEB journal 2019-04, Vol.33 (4), p.5399-5410 |
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| creator | Zhang, Tan Han, Weiqi Zhao, Kangxian Yang, Wanlei Lu, Xuanyuan Jia, Yewei Qin, An Qian, Yu |
| description | ABSTRACTBone fracture healing is a complex, dynamic process that involves various cell types, with osteoclasts and osteoblasts playing indispensable roles. In this study, we found that psoralen, the main active ingredient in Psoralea corylifolia L. fruit extract, enhanced bone fracture healing through activation of osteoclast and osteoblast activity via the ERK signaling pathway. In detail, psoralen promoted receptor activator of nuclear factor‐κB ligand‐induced osteoclastogenesis, mRNA expression of osteoclast‐specific genes, and osteoclastic bone resorption in primary bone marrow‐derived macrophages. Meanwhile, psoralen induced osteogenic differentiation by promoting the mRNA expression of the osteoblast differentiation markers alkaline phosphatase, runt‐related transcription factor 2, osterix, and osteocalcin. At the molecular level, psoralen preferentially activated ERK1/2 but not JNK or p38 MAPKs. Further experiments revealed that psoralen‐induced osteoclast and osteoblast differentiation was abrogated by a specific inhibitor of phosphorylated ERK. In addition, psoralen accelerated bone fracture healing in a rat tibial fracture model, and the numbers of osteoclasts and osteoblasts were increased in psoralen‐treated fracture callus. Taken together, our findings indicate that psoralen accelerates bone fracture healing through activation of osteoclasts and osteoblasts via ERK signaling and has potential as a novel drug in the orthopedic clinic for the treatment of bone fractures.—Zhang, T., Han, W., Zhao, K., Yang, W., Lu, X., Jia, Y., Qin, A., Qian, Y. Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts. FASEB J. 33, 5399–5410 (2019). www.fasebj.org |
| doi_str_mv | 10.1096/fj.201801797R |
| format | Article |
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In this study, we found that psoralen, the main active ingredient in Psoralea corylifolia L. fruit extract, enhanced bone fracture healing through activation of osteoclast and osteoblast activity via the ERK signaling pathway. In detail, psoralen promoted receptor activator of nuclear factor‐κB ligand‐induced osteoclastogenesis, mRNA expression of osteoclast‐specific genes, and osteoclastic bone resorption in primary bone marrow‐derived macrophages. Meanwhile, psoralen induced osteogenic differentiation by promoting the mRNA expression of the osteoblast differentiation markers alkaline phosphatase, runt‐related transcription factor 2, osterix, and osteocalcin. At the molecular level, psoralen preferentially activated ERK1/2 but not JNK or p38 MAPKs. Further experiments revealed that psoralen‐induced osteoclast and osteoblast differentiation was abrogated by a specific inhibitor of phosphorylated ERK. In addition, psoralen accelerated bone fracture healing in a rat tibial fracture model, and the numbers of osteoclasts and osteoblasts were increased in psoralen‐treated fracture callus. Taken together, our findings indicate that psoralen accelerates bone fracture healing through activation of osteoclasts and osteoblasts via ERK signaling and has potential as a novel drug in the orthopedic clinic for the treatment of bone fractures.—Zhang, T., Han, W., Zhao, K., Yang, W., Lu, X., Jia, Y., Qin, A., Qian, Y. Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts. FASEB J. 33, 5399–5410 (2019). www.fasebj.org</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.201801797R</identifier><identifier>PMID: 30702934</identifier><language>eng</language><publisher>United States: Federation of American Societies for Experimental Biology</publisher><subject>Animals ; Bone Marrow Cells - metabolism ; bone repair ; Bone Resorption - drug therapy ; Bone Resorption - metabolism ; Cell Differentiation - drug effects ; Core Binding Factor Alpha 1 Subunit - metabolism ; ERK signaling pathway ; Female ; Ficusin - pharmacology ; Fracture Healing - drug effects ; Macrophages - drug effects ; Macrophages - metabolism ; natural products ; NF-kappa B - metabolism ; NFATC Transcription Factors - metabolism ; osteoblastogenesis ; Osteoblasts - drug effects ; Osteoblasts - metabolism ; osteoclastogenesis ; Osteoclasts - drug effects ; Osteoclasts - metabolism ; Osteogenesis - drug effects ; p38 Mitogen-Activated Protein Kinases - metabolism ; RANK Ligand - metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction - drug effects ; Tartrate-Resistant Acid Phosphatase - metabolism</subject><ispartof>The FASEB journal, 2019-04, Vol.33 (4), p.5399-5410</ispartof><rights>FASEB</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.201801797R$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.201801797R$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30702934$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Tan</creatorcontrib><creatorcontrib>Han, Weiqi</creatorcontrib><creatorcontrib>Zhao, Kangxian</creatorcontrib><creatorcontrib>Yang, Wanlei</creatorcontrib><creatorcontrib>Lu, Xuanyuan</creatorcontrib><creatorcontrib>Jia, Yewei</creatorcontrib><creatorcontrib>Qin, An</creatorcontrib><creatorcontrib>Qian, Yu</creatorcontrib><title>Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>ABSTRACTBone fracture healing is a complex, dynamic process that involves various cell types, with osteoclasts and osteoblasts playing indispensable roles. In this study, we found that psoralen, the main active ingredient in Psoralea corylifolia L. fruit extract, enhanced bone fracture healing through activation of osteoclast and osteoblast activity via the ERK signaling pathway. In detail, psoralen promoted receptor activator of nuclear factor‐κB ligand‐induced osteoclastogenesis, mRNA expression of osteoclast‐specific genes, and osteoclastic bone resorption in primary bone marrow‐derived macrophages. Meanwhile, psoralen induced osteogenic differentiation by promoting the mRNA expression of the osteoblast differentiation markers alkaline phosphatase, runt‐related transcription factor 2, osterix, and osteocalcin. At the molecular level, psoralen preferentially activated ERK1/2 but not JNK or p38 MAPKs. Further experiments revealed that psoralen‐induced osteoclast and osteoblast differentiation was abrogated by a specific inhibitor of phosphorylated ERK. In addition, psoralen accelerated bone fracture healing in a rat tibial fracture model, and the numbers of osteoclasts and osteoblasts were increased in psoralen‐treated fracture callus. Taken together, our findings indicate that psoralen accelerates bone fracture healing through activation of osteoclasts and osteoblasts via ERK signaling and has potential as a novel drug in the orthopedic clinic for the treatment of bone fractures.—Zhang, T., Han, W., Zhao, K., Yang, W., Lu, X., Jia, Y., Qin, A., Qian, Y. Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts. FASEB J. 33, 5399–5410 (2019). www.fasebj.org</description><subject>Animals</subject><subject>Bone Marrow Cells - metabolism</subject><subject>bone repair</subject><subject>Bone Resorption - drug therapy</subject><subject>Bone Resorption - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Core Binding Factor Alpha 1 Subunit - metabolism</subject><subject>ERK signaling pathway</subject><subject>Female</subject><subject>Ficusin - pharmacology</subject><subject>Fracture Healing - drug effects</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - metabolism</subject><subject>natural products</subject><subject>NF-kappa B - metabolism</subject><subject>NFATC Transcription Factors - metabolism</subject><subject>osteoblastogenesis</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - metabolism</subject><subject>osteoclastogenesis</subject><subject>Osteoclasts - drug effects</subject><subject>Osteoclasts - metabolism</subject><subject>Osteogenesis - drug effects</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>RANK Ligand - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Signal Transduction - drug effects</subject><subject>Tartrate-Resistant Acid Phosphatase - metabolism</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1PwkAQhjdGI4gevZr-geLsR7e78aRE_AiJBvXgqZndTqWktKRbNPx7EVROk2feJ5PMy9g5hyEHqy-L-VAAN8BTm04PWJ8nEmJtNByyPhgrYq2l6bGTEOYAwIHrY9aTkIKwUvXZ-3NoWqyojtB7qqjFjkLkmpqiokXfrVqKZoRVWX9Ebr2RuvITuy013SxqQkeNrzB0IcI637Hb8ik7KrAKdPY7B-xtfPs6uo8nT3cPo-tJvOQapnGupMsdokiTwijlkDQJbgVysh58DtoiKJlw60whEklSFcYnPOXO50IJOWAXu7vLlVtQni3bcoHtOvv7cSNc7YSvsqL1f84h-ykwK-bZvsBs_HIjxo_7hfwGm3dmSg</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Zhang, Tan</creator><creator>Han, Weiqi</creator><creator>Zhao, Kangxian</creator><creator>Yang, Wanlei</creator><creator>Lu, Xuanyuan</creator><creator>Jia, Yewei</creator><creator>Qin, An</creator><creator>Qian, Yu</creator><general>Federation of American Societies for Experimental Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>201904</creationdate><title>Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts</title><author>Zhang, Tan ; Han, Weiqi ; Zhao, Kangxian ; Yang, Wanlei ; Lu, Xuanyuan ; Jia, Yewei ; Qin, An ; Qian, Yu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p160R-d43bdbaa275f844bae6e2192a1e9c0cd069a043519b8f253e34f8c5171bcd2423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Bone Marrow Cells - metabolism</topic><topic>bone repair</topic><topic>Bone Resorption - drug therapy</topic><topic>Bone Resorption - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Core Binding Factor Alpha 1 Subunit - metabolism</topic><topic>ERK signaling pathway</topic><topic>Female</topic><topic>Ficusin - pharmacology</topic><topic>Fracture Healing - drug effects</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - metabolism</topic><topic>natural products</topic><topic>NF-kappa B - metabolism</topic><topic>NFATC Transcription Factors - metabolism</topic><topic>osteoblastogenesis</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - metabolism</topic><topic>osteoclastogenesis</topic><topic>Osteoclasts - drug effects</topic><topic>Osteoclasts - metabolism</topic><topic>Osteogenesis - drug effects</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>RANK Ligand - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Signal Transduction - drug effects</topic><topic>Tartrate-Resistant Acid Phosphatase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Tan</creatorcontrib><creatorcontrib>Han, Weiqi</creatorcontrib><creatorcontrib>Zhao, Kangxian</creatorcontrib><creatorcontrib>Yang, Wanlei</creatorcontrib><creatorcontrib>Lu, Xuanyuan</creatorcontrib><creatorcontrib>Jia, Yewei</creatorcontrib><creatorcontrib>Qin, An</creatorcontrib><creatorcontrib>Qian, Yu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Tan</au><au>Han, Weiqi</au><au>Zhao, Kangxian</au><au>Yang, Wanlei</au><au>Lu, Xuanyuan</au><au>Jia, Yewei</au><au>Qin, An</au><au>Qian, Yu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2019-04</date><risdate>2019</risdate><volume>33</volume><issue>4</issue><spage>5399</spage><epage>5410</epage><pages>5399-5410</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>ABSTRACTBone fracture healing is a complex, dynamic process that involves various cell types, with osteoclasts and osteoblasts playing indispensable roles. In this study, we found that psoralen, the main active ingredient in Psoralea corylifolia L. fruit extract, enhanced bone fracture healing through activation of osteoclast and osteoblast activity via the ERK signaling pathway. In detail, psoralen promoted receptor activator of nuclear factor‐κB ligand‐induced osteoclastogenesis, mRNA expression of osteoclast‐specific genes, and osteoclastic bone resorption in primary bone marrow‐derived macrophages. Meanwhile, psoralen induced osteogenic differentiation by promoting the mRNA expression of the osteoblast differentiation markers alkaline phosphatase, runt‐related transcription factor 2, osterix, and osteocalcin. At the molecular level, psoralen preferentially activated ERK1/2 but not JNK or p38 MAPKs. Further experiments revealed that psoralen‐induced osteoclast and osteoblast differentiation was abrogated by a specific inhibitor of phosphorylated ERK. In addition, psoralen accelerated bone fracture healing in a rat tibial fracture model, and the numbers of osteoclasts and osteoblasts were increased in psoralen‐treated fracture callus. Taken together, our findings indicate that psoralen accelerates bone fracture healing through activation of osteoclasts and osteoblasts via ERK signaling and has potential as a novel drug in the orthopedic clinic for the treatment of bone fractures.—Zhang, T., Han, W., Zhao, K., Yang, W., Lu, X., Jia, Y., Qin, A., Qian, Y. Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts. FASEB J. 33, 5399–5410 (2019). www.fasebj.org</abstract><cop>United States</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>30702934</pmid><doi>10.1096/fj.201801797R</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals Bone Marrow Cells - metabolism bone repair Bone Resorption - drug therapy Bone Resorption - metabolism Cell Differentiation - drug effects Core Binding Factor Alpha 1 Subunit - metabolism ERK signaling pathway Female Ficusin - pharmacology Fracture Healing - drug effects Macrophages - drug effects Macrophages - metabolism natural products NF-kappa B - metabolism NFATC Transcription Factors - metabolism osteoblastogenesis Osteoblasts - drug effects Osteoblasts - metabolism osteoclastogenesis Osteoclasts - drug effects Osteoclasts - metabolism Osteogenesis - drug effects p38 Mitogen-Activated Protein Kinases - metabolism RANK Ligand - metabolism Rats Rats, Sprague-Dawley Signal Transduction - drug effects Tartrate-Resistant Acid Phosphatase - metabolism |
| title | Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts |
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