title: Transforming growth factor-β1 (TGF-β1) induces mouse precartilaginous stem cell proliferation through TGF-β receptor II (TGFRII)-Akt-β-catenin signaling.
abstract: Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We successfully purified and primary-cultured PSCs from the neonate mice' perichondrial mesenchyme, and their phenotype was confirmed by the PSC marker fibroblast growth factor receptor-3 (FGFR-3) overexpression. We found that TGF-β1 induced Akt-glycogen synthase kinase-3β (GSK3β) phosphorylation and β-catenin nuclear translocation in the mouse PSCs, which was almost blocked by TGF-β receptor-II (TGFRII) shRNA knockdown. Further, perifosine and MK-2206, two Akt-specific inhibitors, suppressed TGF-β1-induced GSK3β phosphorylation and β-catenin nuclear translocation. Akt inhibitors, as well as β-catenin shRNA knockdown largely inhibited TGF-β1-stimulated cyclin D1/c-myc gene transcription and mouse PSC proliferation. Based on these results, we suggest that TGF-β1 induces Akt activation to promote β-catenin nuclear accumulation, which then regulates cyclin D1/c-myc gene transcription to eventually promote mouse PSC proliferation.
authors.affiliation: Department of Orthopedics, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China. zhangruiwx11@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Orthopedics, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China. chengyuzhangas@126.com.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China. dingdingfl163@163.com.
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China. Jianzou126@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Orthopedics, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China. wuxiwangjunfang@yeah.net.
authors.forename: Junfang
authors.initials: J
authors.lastname: Wang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000502:physiology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D053773:Transforming Growth Factor beta1; D051176:beta Catenin; D019938:Cyclin D1; C496366:Fgfr3 protein, mouse; D051498:Receptor, Fibroblast Growth Factor, Type 3; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3