MicroRNAs in the skeleton: Cell-restricted or potent intercellular communicators?

• MicroRNAs affect cell proliferation, differentiation and apoptosis of bone cells.
• MicroRNAs repress many master genes affecting osteoblast and osteoclast function.
• MicroRNAs are circulating, either bound to proteins or inside extracellular vesicles.
• MicroRNAs have a paracrine signaling function within the bone microenvironment.

MicroRNAs (miRNAs) play a fundamental role in cell proliferation, differentiation and apoptosis and have been associated with many diseases and physiological states. Within the skeleton, both the bone forming cells, osteoblasts, and the bone degrading cells, osteoclasts, are mostly being stimulated by miRNAs through downregulation of inhibitors of bone cell differentiation. Besides miRNAs affecting master genes of bone cell differentiation and function in a cell-restricted manner, evidence is gathering that miRNAs are excreted into the local environment but also into the circulation, implicating a role for miRNAs in nearby or even distant target cells. In this review, the most recent novel miRNAs implicated in bone cell differentiation regulation will be described but also their potential paracrine or endocrine role, thus reinforcing the concept that miRNAs may function as powerful communicators between cell types or tissues.