Long noncoding RNA ZFAS1 suppresses osteogenic differentiation of bone marrow-derived mesenchymal stem cells by upregulating miR-499-EPHA5 axis

Abstract

Emerging evidence suggests that the shift between osteogenic and adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) determines bone mass. Our study was aimed at testing whether a long noncoding RNA called zinc finger antisense 1 (ZFAS1) participates in the differentiation commitment of BMSCs during osteoporosis. We found that ZFAS1 expression was downregulated during osteogenic differentiation and upregulated during adipogenic differentiation. ZFAS1 knockdown facilitated osteogenic differentiation and suppressed adipogenic differentiation. Furthermore, ZFAS1 knockdown suppressed cell senescence and promoted autophagy. Ovariectomized mice injected with a ZFAS1 knockdown construct showed increased bone mass. Mechanismly, ZFAS1 affected the osteogenic and adipogenic differentiation of BMSCs through sponging miR-499 thereby upregulating ephrin type-A receptor 5 (EPHA5). Taken together, our results revealed that the ZFAS1–miR-499–EPHA5 axis may be important for the osteoporosis-related switch between the osteogenesis and adipogenesis of BMSCs, indicating that ZFAS1 represents a plausible therapeutic target for reversing osteoporotic bone loss.