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Platelet-derived growth factor-BB (PDGF-BB) is a clinically proven growth factor during bone regeneration process with unclear mechanisms. Fibroblasts in periodontal ligament (PDL) are considered to be mechanosensitive under orthodontic force. Thus, we established OTM model to investigate the correlation between PDGF-BB and fibroblasts during bone regeneration at tension side. We confirmed that tensile force stimulated PDL cells to induce osteogenic differentiation via Runx-2, OCN up-regulation, and to accelerate new bone deposition along the periodontium and the alveolar bone interface. Interestingly, PDGF-BB level was remarkably enhanced at tension side during OTM in parallel with up-regulated PDGFR\u03b2+\/\u03b1-SMA+ fibroblasts in PDL by immunohistochemistry. Moreover, orthodontic force-treated primary fibroblasts from PDL were isolated and, cultured in vitro, which showed similar morphology and phenotype with control fibroblasts without OTM treatment. PDGFR\u03b2 expression was confirmed to be increased in orthodontic force-treated fibroblasts by immunofluorescence and flow cytometry. Bioinformatics analysis identified that PDGF-BB\/PDGFR\u03b2 signals were relevant to the activation of JAK\/STAT3 signals. The protein expression of JAK2 and STAT3 was elevated in PDL of tension side. Importantly, in vivo, the treatment of the inhibitors (imatinib and AG490) for PDGFR\u03b2 and JAK\u2013STAT signals were capable of attenuating the tooth movement. The osteogenic differentiation and bone regeneration in tension side were down-regulated upon the treatment of inhibitors during OTM. Meanwhile, the expressions of PDGFR\u03b2, JAK2 and STAT3 were inhibited by imatinib and AG490. Thus, we concluded that tensile force-induced PDGF-BB activated JAK2\/STAT3 signals in PDGFR\u03b2<jats:sup>+<\/jats:sup> fibroblasts in bone formation during OTM.<\/jats:p>","DOI":"10.1038\/s41598-020-68068-1","type":"journal-article","created":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T10:06:38Z","timestamp":1594289198000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Tensile force-induced PDGF-BB\/PDGFR\u03b2 signals in periodontal ligament fibroblasts activate JAK2\/STAT3 for orthodontic tooth movement"],"prefix":"10.1038","volume":"10","author":[{"given":"Yuqin","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxian","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"68068_CR1","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1038\/s41586-018-0650-9","volume":"563","author":"RC Ransom","year":"2018","unstructured":"Ransom, R. 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