As a systemic disease, osteoporosis causes decreased bone density and microdamage to bone structures, subsequently leading to a high risk of bone fractures.43 Elucidating the pathogenesis and then developing novel therapies for OP are critical areas in this field.44 Dysfunction of MSCs, the major origin of osteoblasts, in osteogenesis was demonstrated to contribute to OP pathogenesis, but the detailed mechanism still needs further investigation.45,46 In our study, we showed that BRD4 expression was downregulated in OP-MSCs, and BRD4-CKO mice exhibited a disease phenotype similar to OP. This evidence concerns the gene BRD4 and osteoporosis.