MicroRNAs regulating TGFβ and BMP signaling in the osteoblast lineage.

This review showcases miRNAs contributing to the regulation of bone forming osteoblasts through their effects on the TGFβ and BMP pathways, with a focus on ligands, receptors and SMAD-mediated signaling. The goal of this work is to provide a basis for broadly understanding the contribution of miRNAs to the modulation of TGFβ and BMP signaling in the osteoblast lineage, which may provide a rationale for potential therapeutic strategies. Therefore, the search strategy for this review was restricted to validated miRNA-target interactions within the canonical TGFβ and BMP signaling pathways; miRNA-target interactions based only bioinformatics are not presented. Specifically, this review discusses miRNAs targeting each of the TGFβ isoforms, as well as BMP2 and BMP7. Further, miRNAs targeting the signaling receptors TGFβR1 and TGFβR2, and those targeting the type 1 BMP receptors and BMPR2 are described. Lastly, miRNAs targeting the receptor SMADs, the common SMAD4 and the inhibitory SMAD7 are considered. Of these miRNAs, the miR-140 family plays a prominent role in inhibiting TGFβ signaling, targeting both ligand and receptor. Similarly, the miR-106 isoforms target both BMP2 and SMAD5 to inhibit osteoblastic differentiation. Many of the miRNAs targeting TGFβ and BMP signaling components are induced during fracture, mechanical unloading or estrogen deprivation. Localized delivery of miRNA-based therapeutics that modulate the BMP signaling pathway could promote bone formation.