Gene Regulation and Systems Biology

Salla Suomi^1,5, Hanna Taipaleenmäki^2,5, Anne Seppänen¹, Tommi Ripatti^3,4, Kalervo Väänänen¹, Teuvo Hentunen¹, Anna-Marja Säämänen² and Tiina Laitala-Leinonen¹

¹Bone Biology Research Consortium, Department of Anatomy, ²Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Turku, FI-20520, Finland. ³Department of Molecular Medicine, National Public Health Institute of Finland. ⁴Genome Informatics Unit, Biomedicum Helsinki, FI-00290, Finland. ⁵These authors contributed equally to this work.

Abstract

MicroRNAs (miRNAs) are non-coding RNAs that bind to target mRNA leading to translational arrest or mRNA degradation. To study miRNA-mediated regulation of osteogenesis and chondrogenesis, we compared the expression of 35 miRNAs in osteoblasts and chondroblasts derived from mouse marrow stromal cells (MSCs). Differentiation of MSCs resulted in up- or downregulation of several miRNAs, with miR-199a expression being over 10-fold higher in chondroblasts than in undifferentiated MSCs. In addition, miR-124a was strongly upregulated during chondrogenesis while the expression of miR-96 was substantially suppressed. A systems biological analysis of the potential miRNA target genes and their interaction networks was combined with promoter analysis. These studies link the differentially expressed miRNAs to collagen synthesis and hypoxia, key pathways related to bone and cartilage physiology. The global regulatory networks described here suggest for the first time how miRNAs and transcription factors are capable of fi ne-tuning the osteogenic and chondrogenic differentiation of mouse MSCs.