DEC1 deficiency protects against bone loss induced by ovariectomy through inhibiting inflammation.

Abstract

Previous studies have shown that differentiated embryo-chondrocyte expressed gene 1 (DEC1) promotes osteoblast osteogenesis. To investigate the role of DEC1 in postmenopausal osteoporosis (PMOP), we utilized the two types (DEC1 ^+/+, DEC1 ^-/-) mice to establish an ovariectomy (OVX) model and found that the bone loss in DEC1 ^-/- OVX mice were much less than that in DEC1 ^+/+ OVX mice. The expression levels of RUNX2 and OSX significantly increased in DEC1 ^-/- OVX mice compared with those in DEC1 ^+/+ OVX mice. Whereas, NFATc1, c-Fos, CTSK and RANKL/OPG significantly decreased in DEC1 ^-/- OVX mice compared with those in DEC1 ^+/+ OVX mice. Likewise, DEC1 deficiency suppressed IL-6 and IL-1β. Further study showed Runx2, Osx, Alp, and Ocn significantly increased in DEC1 ^-/- OVX BMSCs compared with those in DEC1 ^+/+ OVX BMSCs. And the mRNA levels of IL-1β, IL-6, Tnf-α and Ifn-γ increased significantly in DEC1 ^+/+ OVX BMMs compared with those in DEC1 ^+/+ sham BMMs, but not in DEC1 ^-/- OVX BMMs compared with those in DEC1 ^-/- sham BMMs. Furthermore, the p-IκBα and p-P65 significantly increased in DEC1 ^+/+ OVX BMMs compared with those in DEC1 ^+/+ sham BMMs, but did not increase in DEC1 ^-/- OVX BMMs compared with those in DEC1 ^-/- sham BMMs. Taken together, DEC1 deficiency inhibits the NF-κB pathway induced by OVX, thereby decreasing cytokines, and subsequently, inhibits the decrease of osteogenesis and the increase of osteoclastogenesis caused by OVX. The findings provide a novel understanding of postmenopausal osteoporosis development, which offers potential avenues for the intervention strategies.