We have previously demonstrated that DEC1 promotes osteoblast differentiation. This study aims to evaluate the impact of DEC1 knockout on osteopenic activities, such as osteoclast differentiation and the expression of bone-degrading genes. To gain mechanistic insights, we employed both in vivo and in vitro experiments, utilizing cellular and molecular approaches, including osteoclast differentiation assays and RNA-seq in combination with ChIP-seq. Our results showed that NFATc1, a master regulator of osteoclast differentiation, and PPP3CB, a member of the calcineurin family, were significantly upregulated in DEC1