Irisin, induced by physical exercise or administered directly, can help to reverse FNDC5 and irisin downregulation to facilitate osteoblast function and bone formation.257 Exosomal miR-21-5p from BMSCs could promote osteoblastic differentiation and ameliorate osteoporosis by interacting with KLF3.258 In osteoclasts, activating transcription factor 1 (ATF1) can activate miR-214-5p transcriptionally and reduce the expression of ITGA7, thus contributing to osteoclastogenesis and altering OVX-induced bone absorption.259. This evidence concerns the gene FNDC5 and osteoporosis.