Frontiers in Pharmacology (May 2020)
Long Noncoding RNA GAS5 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating GDF5 and p38/JNK Signaling Pathway
Abstract
Both extracellular matrix (ECM) and stem cells contribute to the formation of bones. Accumulating evidence proved that the growth differentiation factor 5 (GDF5) plays a vital role in ECM osteogenesis regulation; the use of human periodontal ligament stem cells (hPDLSCs) may contribute to alveolar bone regeneration. Moreover, long noncoding RNAs (lncRNA) serves as a regulator in the growing process of cellular organisms including bone formation. Previous efforts has led us to the discovery that the expression of growth arrest specific transcript 5 (GAS5) changed in the osteogenic differentiation of hPDLSCs. Moreover, the expression of GAS5, as it turns out, is correlated to GDF5. This study attempts to investigate the inner workings of GAS5 in its regulation of osteoblastic differentiation of hPDLSCs. Cell transfection, Alkaline phosphatase (ALP) staining, Alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining analysis and western blotting were employed in this study. It came to our notice that GAS5 and GDF5 expression increased during osteogenesis induction of hPDLSCs. Knocking down of GAS5 inhibited the osteogenic differentiation of hPDLSCs, whereas overexpressing GAS5 promoted these effects. Molecular mechanism study further demonstrated that overexpressing GAS5 bolsters GDF5 expression and boosts the phosphorylation of JNK and p38 in hPDLSCs, with opposite effects in GAS5 knockdown group. To sum up, long noncoding RNA GAS5 serves to regulate the osteogenic differentiation of PDLSCs via GDF5 and p38/JNK signaling pathway. Our findings expand the theoretical understanding of the osteogenesis mechanism in hPDLSCs, providing new insights into the treatment of bone defects.
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