Authors: Sudharsan Periyasamy-Thandavan, John Burke, Bharati Mendhe, Galina Kondrikova, Ravindra Kolhe, Monte Hunter, Carlos M Isales, Mark W Hamrick, William D Hill, Sadanand Fulzele
Summary: Stromal cell-derived factor 1 (SDF-1 or CXCL12), is a cytokine secreted by cells including bone marrow stromal cells (BMSC). SDF-1 plays a vital role in BMSC migration, survival, and differentiation. Our group previously reported the role of SDF-1 in osteogenic differentiation in vitro and bone formation in vivo; however, our understanding of the post-transcriptional regulatory mechanism of SDF-1 remains poor. microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate the messenger RNAs (mRNAs) of protein-coding genes. In this study, we aimed to investigate the impact of miR-141-3p on SDF-1 expression in BMSCs and its importance in the aging bone marrow microenvironment. Our data demonstrated that murine and human BMSCs expressed miR-141-3p that repressed SDF-1 gene expression at the functional level (luciferase reporter assay) by targeting the 3′-untranslated region (3’-UTR) of mRNA. We also found that transfection of miR-141-3p decreased osteogenic markers in human BMSCs. Our results demonstrate that miR-141-3p expression increases with age, while SDF-1 decreases in both the human and mouse bone marrow niche. Taken together, these results support that miR-141-3p is a novel regulator of SDF-1 in bone cells and plays an important role in the age dependent pathophysiology of murine and human bone marrow niche.
Source: The Journals of Gerontology: Series A, 2018