title: IGF1 potentiates BMP9-induced osteogenic differentiation in mesenchymal stem cells through the enhancement of BMP/Smad signaling.
abstract: Engineered bone tissue is thought to be the ideal alternative for bone grafts in the treatment of related bone diseases. BMP9 has been demonstrated as one of the most osteogenic factors, and enhancement of BMP9-induced osteogenesis will greatly accelerate the development of bone tissue engineering. Here, we investigated the effect of insulin-like growth factor 1 (IGF1) on BMP9-induced osteogenic differentiation, and unveiled a possible molecular mechanism underling this process. We found that IGF1 and BMP9 are both detectable in mesenchymal stem cells (MSCs). Exogenous expression of IGF1 potentiates BMP9-induced alkaline phosphatase (ALP), matrix mineralization, and ectopic bone formation. Similarly, IGF1 enhances BMP9-induced endochondral ossification. Mechanistically, we found that IGF1 increases BMP9-induced activation of BMP/Smad signaling in MSCs. Our findings demonstrate that IGF1 can enhance BMP9-induced osteogenic differentiation in MSCs, and that this effect may be mediated by the enhancement of the BMP/Smad signaling transduction triggered by BMP9. [BMB Reports 2016; 49(2): 122-127].
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Ran-Xi
authors.initials: RX
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Pi
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Liang-Jun
authors.initials: LJ
authors.lastname: Yin
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Deng
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D055427:Growth Differentiation Factor 2 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D053495:Osteopontin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D015415:Biomarkers; D055427:Growth Differentiation Factor 2; D051785:Smad Proteins; D053495:Osteopontin; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase