Mesenchymal stem cells (MSCs) are capable of differentiating into a wide range of cell types including those associated with the bone development and maintenance (osteoblasts, osteocytes), cartilage, tendons, muscle, adipose, and more. The pluripotent nature of MSCs makes them a potentially valuable tool in therapeutics, particularly in the fields of disease (e.g. osteogenesis imperfecta), tissue repair and regeneration.
The molecular mechanisms underlying MSC differentiation are poorly understood. Microarray profiling studies have clearly identified genomic profiles that distinguish mother and daughter cell lineages, yet the triggers that orchestrate these processes have not been identified.
RNA interference (RNAi) is a near-ubiquitous pathway involved in post-transcriptional gene modulation. A key effector molecule of RNAi is the microRNA (miRNA or miR). These small, non-coding RNAs are transcribed as primary miRNAs (pri-miRNA) and processed in the nucleus by Drosha (a Type III ribonuclease) to generate short hairpin structures referred to as pre-miRNAs. The resulting molecules are transported to the cytoplasm and processed by a second nuclease (Dicer) before being incorporated into the RNA Induced Silencing Complex (RISC). Interaction between the mature miRNA-RISC complex and messenger RNA (mRNA), particularly between the seed region of the miRNA guide strand (nucleotides 2-7) and regions of the 3′ UTR of the mRNA, leads to gene knockdown by transcript cleavage and/or translation attenuation.