MiR-214 is an important regulator of the musculoskeletal metabolism and disease

MiR-214 belongs to a family of microRNA (small, highly conserved noncoding RNA molecules) precursors that play a pivotal role in biological functions, such as cellular function, tissue development, tissue homeostasis, and pathogenesis of diseases. Recently, miR-214 emerged as a critical regulator of musculoskeletal metabolism. Specifically, miR-214 can mediate skeletal muscle myogenesis and vascular smooth muscle cell proliferation, migration, and differentiation. MiR-214 also modulates osteoblast function by targeting specific molecular pathways and the expression of various osteoblast-related genes; promotes osteoclast activity by targeting phosphatase and tensin homolog (Pten); and mediates osteoclast-osteoblast intercellular crosstalk via an exosomal miRNA paracrine mechanism. Importantly, dysregulation in miR-214 expression is associated with pathological bone conditions such as osteoporosis, osteosarcoma, multiple myeloma, and osteolytic bone metastasis of breast cancer. This review discusses the cellular targets of miR-214 in bone, the molecular mechanisms governing the activities of miR-214 in the musculoskeletal system, and the putative role of miR-214 in skeletal diseases. Understanding the biology of miR-214 could potentially lead to the development of miR-214 as a possible biomarker and a therapeutic target for musculoskeletal diseases. Highlights MiR-214 is an important regulator of the musculoskeletal system and is involved in muscle development, bone homeostasis and bone-related disorders. MiR-214 is able to mediate skeletal muscle myogenesis and vascular smooth muscle cell proliferation, migration and differentiation. MiR-214 modulates osteoblast function by targeting specific molecular pathways and the expression of various osteoblast-related genes. MiR-214 promotes osteoclast activity by targeting specific genes and mediates osteoblast-osteoclast intercellular crosstalk via an exosomal miRNA paracrine mechanism. Dysregulation in miR-214 expression has been associated with bone diseases such as osteoporosis, osteosarcoma and multiple myeloma. Osteoclastic miR-214 is involved in regulating osteoclast-mediated osteolytic bone metastasis of breast cancer.