All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts.
All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts.
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全反式视黄酸将罗格列酮诱导的小鼠胚胎成纤维细胞的脂肪形成分化转变为成骨分化
DOI：
10.3892/ijmm.2016.2782
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发表时间：
2016-12
影响因子：
5.4
通讯作者：
He BC
中科院分区：
文献类型：
--
作者：
Shao Y;Chen QZ;Zeng YH;Li Y;Ren WY;Zhou LY;Liu RX;Wu K;Yang JQ;Deng ZL;Yu Y;Sun WJ;He BC
Rosiglitazone (RSG) is a potent drug used in the treatment of insulin resistance; however, it is associated with marked skeletal toxicity. RSG-induced osteoporosis may contribute to the promotion of adipogenic differentiation at the expense of osteogenic differentiation in bone marrow stromal cells. The aim of this study was to investigate whether RSG-induced bone toxicity can be reversed by combined treatment with all-trans retinoic acid (ATRA). We examined different osteogenic markers in mouse embryonic fibroblasts (MEFs) following treatment with RSG, ATRA, or RSG and ATRA in combination. We examined the effects of RSG and/or ATRA on ectopic bone formation, and dissected the possible molecular mechanisms underlying this process. We found that ATRA or RSG both induced alkaline phosphatase (ALP) activity in the MEFs, and that the ATRA-induced ALP activity was enhanced by RSG and vice versa. However, only the combination of RSG and ATRA increased the expression of osteopontin and osteocalcin, promoted matrix mineralization, and induced ectopic ossification in MEFs. Mechanistically, we found that the osteogenic differentiation induced by the combination of RSG and ATRA may be mediated partly by suppressing RSG-induced adipogenic differentiation and activating bone morphogenetic protein (BMP)/Smad signaling. On the whole, our findings demonstrate that RSG in combination with ATRA promotes the commitment of MEFs to the osteoblast lineage. Thus, the combination of these two agents may prove to be a promising and novel therapeutic regimen for insulin resistance without skeletal toxicity. It may also be a better strategy with which to prevent RSG-induced osteoporosis.
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影响因子：
4.3
作者：
Lecka-Czernik, Beata
通讯作者：
Lecka-Czernik, Beata
影响因子：
64.5
作者：
Duester G
通讯作者：
Duester G
影响因子：
4.8
作者：
Ali, AA;Weinstein, RS;Jilka, RL
通讯作者：
Jilka, RL
影响因子：
7.7
作者：
Felipe, F;Bonet, ML;Palou, A
通讯作者：
Palou, A
影响因子：
5.3
作者：
Berry, Daniel C.;Noy, Noa
通讯作者：
Noy, Noa