MicroRNA-141-3p Negatively Modulates SDF-1 Expression in Age-Dependent Pathophysiology of Human and Murine Bone Marrow Stromal Cells

Sudharsan Periyasamy-Thandavan, John Burke, Bharati Mendhe, Galina Kondrikova, Ravindra Kolhe, Monte Hunter, Carlos M. Isales, Mark W. Hamrick, William D. Hill, Sadanand Fulzele, Isabel Beerman, Joshua Hare

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Stromal cell-derived factor-1 (SDF-1 or CXCL12) is a cytokine secreted by cells including bone marrow stromal cells (BMSCs). 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 are small noncoding 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 (BM) 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 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 BM 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 BM niche.

Original languageEnglish (US)
Pages (from-to)1368-1374
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume74
Issue number9
DOIs
StatePublished - Aug 16 2019

Keywords

  • Aging
  • Bone marrow stromal cells
  • SDF-1
  • miR-141

ASJC Scopus subject areas

  • General Medicine

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