RRC ID 61989
Author Kaneda-Ikeda E, Iwata T, Mizuno N, Nagahara T, Kajiya M, Ouhara K, Yoshioka M, Ishida S, Kawaguchi H, Kurihara H.
Title Regulation of osteogenesis via miR-101-3p in mesenchymal stem cells by human gingival fibroblasts.
Journal J Bone Miner Metab
Abstract INTRODUCTION:Mesenchymal stem cells (MSCs) can differentiate into various types of cells and can thus be used for periodontal regenerative therapy. However, the mechanism of differentiation is still unclear. Transplanted MSCs are, via their transcription factors or microRNAs (miRNAs), affected by periodontal cells with direct contact or secretion of humoral factors. Therefore, transplanted MSCs are regulated by humoral factors from human gingival fibroblasts (HGF). Moreover, insulin-like growth factor (IGF)-1 is secreted from HGF and regulates periodontal regeneration. To clarify the regulatory mechanism for MSC differentiation by humoral factors from HGF, we identified key genes, specifically miRNAs, involved in this process, and determined their function in MSC differentiation.
MATERIALS AND METHODS:Mesenchymal stem cells were indirectly co-cultured with HGF in osteogenic or growth conditions and then evaluated for osteogenesis, undifferentiated MSC markers, and characteristic miRNAs. MSCs had their miRNA expression levels adjusted or were challenged with IGF-1 during osteogenesis, or both of which were performed, and then, MSCs were evaluated for osteogenesis or undifferentiated MSC markers.
RESULTS:Mesenchymal stem cells co-cultured with HGF showed suppression of osteogenesis and characteristic expression of ETV1, an undifferentiated MSC marker, as well as miR-101-3p. Over-expression of miR-101-3p regulated osteogenesis and ETV1 expression as well as indirect co-culture with HGF. IGF-1 induced miR-101-3p and ETV1 expression. However, IGF-1 did not suppress osteogenesis.
CONCLUSIONS:Humoral factors from HGF suppressed osteogenesis in MSCs. The effect was regulated by miRNAs and undifferentiated MSC markers. miR-101-3p and ETV1 were the key factors and were regulated by IGF-1.
Volume 38(4)
Pages 442-455
Published 2020-7-1
DOI 10.1007/s00774-019-01080-2
PII 10.1007/s00774-019-01080-2
PMID 31970478
MeSH Biomarkers / metabolism Cell Differentiation / drug effects Cell Differentiation / genetics Cells, Cultured Fibroblasts / drug effects Fibroblasts / metabolism* Gingiva / cytology* Humans Insulin-Like Growth Factor I / pharmacology Mesenchymal Stem Cells / drug effects Mesenchymal Stem Cells / metabolism* MicroRNAs / genetics MicroRNAs / metabolism* Osteogenesis / drug effects Osteogenesis / genetics* Transcription Factors / metabolism
IF 2.297
Human and Animal Cells Human mesenchymal stem cells