{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:06:03Z","timestamp":1785798363454,"version":"3.56.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hu'po Anshen decoction (HPASD), a traditional Chinese medicine used to treat concussion and fracture, could regulate the expression of bone morphogenetic protein 2 (BMP2). However, whether HPASD affects the fracture healing of traumatic brain injury (TBI) combined with a fracture through BMP2 and its downstream signals remains obscure. The chondrocyte\u2010specific BMP2 conditional knockout mice and chondrocyte\u2010specific cyclooxygenase\u20102 (COX2) overexpression mice were generated. BMP2 conditional knockout mice were treated with fracture surgery, fracture combined with TBI, or fracture combined with TBI followed by different doses of HPASD (2.4, 4.8, and 9.6\u2009g\/kg), respectively. TBI was induced by Feeney's weight\u2010drop technique. The fracture callus formation and fracture sites were determined by X\u2010ray, micro\u2010CT, and histological analyses. The expressions of chondrocyte\u2010, osteoblast\u2010, and BMP2\/COX2 signal\u2010related targets were determined by quantitative reverse transcription\u2010polymerase chain reaction (qRT\u2010PCR) and western blot assays. The specific absence of BMP2 in chondrocytes led to the prolonged formation of cartilage callus, a delay in the osteogenesis initiation and the downregulation of RUNX2, Smad1\/5\/9, EP4, ERK1\/2, RSK2, ATF4. Overexpression of COX2 partially reverses the effects of chondrocyte\u2010specific BMP2 knockout mice. HPASD promoted cartilage callus formation and osteogenesis initiation, as accompanied by upregulated expression levels of RUNX2, Smad1\/5\/9, EP4, ERK1\/2, RSK2, and ATF4 in a time\u2010dependent and concentration\u2010dependent manner in chondrocyte\u2010specific BMP2 knockout mice. Overall, our findings demonstrated that HPASD induced COX2 transcription through the BMP2\u2010Smad1\/5\/9\u2010RUNX2 axis, and then affected fracture healing through the COX2\u2010mediated EP4\u2010ERK1\/2\u2010RSK2\u2010ATF4 axis.<\/jats:p>","DOI":"10.1096\/fj.202201552rr","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T17:00:48Z","timestamp":1683738048000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hu'po Anshen decoction promotes fracture healing in mice with traumatic brain injury through\n                    <scp>BMP2\u2010COX2\u2010ATF4<\/scp>\n                    signaling pathway"],"prefix":"10.1096","volume":"37","author":[{"given":"WeiHang","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Zhejiang Chinese Medical University  Zhejiang 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