Insulin-like growth factor 1 enhances the proliferation and osteogenic differentiation of human periodontal ligament stem cells via ERK and JNK MAPK pathways.
Insulin-like growth factor 1 (IGF-1) is a potent mitogenic protein which can enhance the osteogenic differentiation of periodontal ligament (PDL) fibroblasts. However, it remains unclear whether IGF-1 can stimulate the osteogenic differentiation and osteogenesis of human periodontal ligament stem cells (PDLSCs). In this study, STRO-1(+) PDLSCs were isolated from human PDL tissues, treated with IGF-1, and their osteogenic capacity was investigated in vitro and in vivo. Dimethyl-thiazol-diphenyl tetrazolium bromide assay and flow cytometry results demonstrated that 10-200 ng/mL IGF-1 can stimulate the proliferation ability of PDLSCs and 100 ng/mL is the optimal concentration. Exogenous IGF-1 can modify the ultrastructure, enhance the alkaline phosphatase activity, the mineralization ability of PDLSCs, and increase the expression of osteogenic markers (runt-related transcription factor 2, osterix, and osteocalcin) at mRNA and protein levels. In vivo transplantation illustrated that IGF-1 treated implants generated more mineralized tissues, and presented stronger expression of RUNX2, OSX, and OCN than control group. Moreover, the expression of phosphor-ERK and phosphor-JNK in these stem cells was upregulated by IGF-1, indicating that MAPK signaling pathway was activated during the osteogenic differentiation of PDLSCs mediated by IGF-1. Together, the results showed that IGF-1 can promote the osteogenic differentiation and osteogenesis of STRO-1(+) PDLSCs via ERK and JNK MAPK pathway, suggesting that IGF-1 is a potent agent for stem cell-based periodontal tissue regeneration.
Institute of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, China.
Yan
Y
Yu
Jinquan
J
Mu
Zhipeng
Z
Fan
Gang
G
Lei
Ming
M
Yan
Sainan
S
Wang
Chunbo
C
Tang
Zilu
Z
Wang
Jinhua
J
Yu
Guangdong
G
Zhang
D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D010012:Osteogenesis; D010513:Periodontal Ligament / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D055815:Young Adult
D007334:Insulin-Like Growth Factor I; D048049:Extracellular Signal-Regulated MAP Kinases