Specifically, mechanical loading directly induced a downregulation of HDAC1 expression, which was involved in the promotion of osteogenic differentiation and bone formation through the targeting of JAG1, a master inducer of osteogenic differentiation.21, 22, 23 Our findings also demonstrate that the therapeutic inhibition of HDAC1 may partly rescue osteoporosis caused by mechanical unloading. Here, JAG1 is linked to osteoporosis.