The role of microRNAs in bone development.

Epigenetic regulation is critical for proper bone development. Evidence from a large body of published literature informs us that microRNAs (miRNAs) are important epigenetic factors that control many aspects of bone development, homeostasis, and repair processes. These small non-coding RNAs function at the post-transcriptional level to suppress expression of specific target genes. Many target genes may be affected by one miRNA resulting in alteration in cellular pathways and networks. Therefore, changes in levels or activity of a specific miRNA (e.g. via genetic mutations, disease scenarios, or by over-expression or inhibition strategies in vitro or in vivo) can lead to substantial changes in cell processes including proliferation, metabolism, apoptosis and differentiation. In this review, Section 1 briefly covers general background information on processes that control bone development as well as the biogenesis and function of miRNAs. In Section 2, we discuss the importance of miRNAs in skeletal development based on findings from in vivo mouse models and human clinical reports. Section 3 focuses on describing more recent data from the last three years related to miRNA regulation of osteoblast differentiation in vitro. Some of these studies also involve utilization of an in vivo rodent model to study the effects of miRNA modulation in scenarios of osteoporosis, bone repair or ectopic bone formation. In Section 4, we provide some recent information from studies analyzing the potential of miRNA-mediated crosstalk in bone and how exosomes containing miRNAs from one bone cell may affect the differentiation or function of another bone cell type. We then conclude by summarizing where the field currently stands with respect to miRNA-mediated regulation of osteogenesis and how information gained from developmental processes can be instructive in identifying potential therapeutic miRNA targets for the treatment of certain bone conditions.