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+/+...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.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82073934 and 81872937 to J.Y.)the Special Foundation for Clinical Science and Technology of Jiangsu Province(Grant No.JX10114120).
文摘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.
