DEC1 deficiency protects against bone loss induced by ovariectomy by inhibiting inflammationOA

Studies have shown that differentiated embryo-chondrocyte expressed gene 1(DEC1)promotes osteoblast osteogenesis.To investigate the role of DEC1 in postmenopausal osteoporosis,we used the two genotypes of mice(Dec1+/+and Dec1-/-)to establish an ovariectomy model and found that the bone loss was significantly lower in Dec1-/-ovariectomy mice than in Dec1+/+ovariectomy mice.The expression levels of RUNX2 and OSX were significantly increased in Dec1-/-ovariectomy mice,compared with Dec1+/+ovariectomy mice;however,the expression levels of NFATc1,c-Fos,CTSK,and RANKL/OPG ratio were significantly decreased in Dec1-/-ovariectomy mice,compared with those in Dec1+/+ovariectomy mice.Likewise,DEC1 deficiency also suppressed the expression levels of IL-6 and IL-1β.Further results showed that the mRNA expression levels of Runx2,Osx,and Alp were significantly increased in bone marrow mesenchymal stem cells of Dec1-/-ovariectomy mice,compared with those of Dec1+/+ovariectomy mice.Moreover,the mRNA levels of Il1b,Il6,Tnfa,and Ifng were significantly increased in bone marrow-derived macrophages(BMMs)of Dec1+/+ovariectomy mice,compared with those of Dec1+/+sham mice,but not in Dec1-/-ovariectomy BMMs,when compared with those in Dec1-/-sham BMMs.Additionally,the expression levels of p-IκBαand p-P65 were significantly increased in Dec1+/+ovariectomy BMMs,compared with those in Dec1+/+sham BMMs,but did not increase in Dec1-/-ovariectomy BMMs,compared with those in Dec1-/-sham BMMs.Taken together,DEC1 deficiency inhibited the NF-κB pathway induced by ovariectomy,thereby decreasing cytokines and subsequently inhibiting the decrease of osteo-genesis and the increase of osteoclastogenesis caused by ovariectomy.The findings may provide a novel under-standing of postmenopausal osteoporosis development,and offer potential avenues for the disease intervention.