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In this study, we found that psoralen, the main active ingredient in\n                    <jats:italic>Psoralea corylifolia L<\/jats:italic>\n                    . fruit extract, enhanced bone fracture healing through activation of osteoclast and osteoblast activity\n                    <jats:italic>via<\/jats:italic>\n                    the ERK signaling pathway. In detail, psoralen promoted receptor activator of nuclear factor\u2010\u03baB ligand\u2010induced osteoclastogenesis, mRNA expression of osteoclast\u2010specific genes, and osteoclastic bone resorption in primary bone marrow\u2010derived macrophages. Meanwhile, psoralen induced osteogenic differentiation by promoting the mRNA expression of the osteoblast differentiation markers alkaline phosphatase, runt\u2010related 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\u2010induced 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\u2010treated fracture callus. Taken together, our findings indicate that psoralen accelerates bone fracture healing through activation of osteoclasts and osteoblasts\n                    <jats:italic>via<\/jats:italic>\n                    ERK signaling and has potential as a novel drug in the orthopedic clinic for the treatment of bone fractures.\u2014Zhang, 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\u20135410 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801797r","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T13:46:27Z","timestamp":1548942387000},"page":"5399-5410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts"],"prefix":"10.1096","volume":"33","author":[{"given":"Tan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangxian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanlei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanyuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yewei","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Key Laboratory of Orthopedic Implants Shanghai Ninth People's Hospital Shanghai Jiaotong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shaoxing People's Hospital Zhejiang University School of Medicine  Shaoxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2072"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/17453674.2017.1321351"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2014.04.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"542","DOI":"10.3111\/13696998.2015.1019887","article-title":"Low\u2010intensity pulsed ultrasound (LIPUS) can decrease the economic burden of fracture non\u2010union","volume":"18","author":"Mehta S.","year":"2015","journal-title":"J. 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