Expression regulation and functional analysis of RGS2 and RGS4 in adipogenic and osteogenic differentiation of human mesenchymal stem cells.
Expression regulation and functional analysis of RGS2 and RGS4 in adipogenic and osteogenic differentiation of human mesenchymal stem cells.
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DOI：
10.1186/s40659-017-0148-1
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发表时间：
2017-12-26
影响因子：
6.7
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Madrigal A;Tan L;Zhao Y
了解骨形成骨细胞和脂质储存脂肪细胞形成的分子基础将有助于深入了解干/祖细胞引起的疾病的原因，并为骨或脂肪相关疾病开发治疗方法。本研究探讨了G蛋白信号调节因子（Regulators of G protein signaling，RGS）家族的两个成员RGS 2和RGS 4在人骨髓间充质干细胞（human mesenchymal stem cells，hMSCs）成脂分化和成骨分化过程中的作用。发现RGS 2和RGS 4的表达在地塞米松（DEX）和3-异丁基-甲基黄嘌呤诱导的脂肪形成期间被反向调节，无论是否存在胰岛素，响应于脂肪形成诱导，RGS 2上调和RGS 4下调。RGS 2表达在成骨过程中也上调，其水平与单独DEX处理诱导的水平相似，DEX是成脂和成骨分化诱导培养基的共同组分，但显著低于成脂诱导培养基诱导的水平。RGS 4的表达下调，在第一个48小时的成骨，但上调后，在这两种情况下，在类似的水平，诱导单独的DEX。使用针对RGS 2的小干扰RNA的表达敲低导致脂肪生成和骨生成期间的分化效率降低。另一方面，RGS 4的表达敲低也导致成脂分化降低，但成骨分化增加。RGS 2和RGS 4在hMSCs成脂和成骨分化过程中的差异调节。此外，RGS 2和RGS 4在脂肪形成过程中发挥积极作用，但在骨形成过程中发挥相反的作用，其中RGS 2作为正调节剂，RGS 4作为负调节剂。这些结果意味着RGS蛋白的成员可能在人类脂肪形成和成骨过程中发挥多方面的作用，以平衡或抵消这些过程中彼此的功能。本文的在线版本（10.1186/s40659-017-0148-1）包含补充材料，可供授权用户使用。
Understanding the molecular basis underlying the formation of bone-forming osteocytes and lipid-storing adipocytes will help provide insights into the cause of disorders originating in stem/progenitor cells and develop therapeutic treatments for bone- or adipose-related diseases. In this study, the role of RGS2 and RGS4, two members of the regulators of G protein signaling (RGS) family, was investigated during adipogenenic and osteogenenic differentiation of human mesenchymal stem cells (hMSCs). Expression of RGS2 and RGS4 were found to be inversely regulated during adipogenesis induced by dexamethasone (DEX) and 3-isobutyl-methylxanthine, regardless if insulin was present, with RGS2 up-regulated and RGS4 down-regulated in response to adipogenic induction. RGS2 expression was also up-regulated during osteogenesis at a level similar to that induced by treatment of DEX alone, a shared component of adipogenic and osteogenic differentiation inducing media, but significantly lower than the level induced by adipogenic inducing media. RGS4 expression was down-regulated during the first 48 h of osteogenesis but up-regulated afterwards, in both cases at levels similar to that induced by DEX alone. Expression knock-down using small interfering RNA against RGS2 resulted in decreased differentiation efficiency during both adipogenesis and osteogenesis. On the other hand, expression knock-down of RGS4 also resulted in decreased adipogenic differentiation but increased osteogenic differentiation. RGS2 and RGS4 are differentially regulated during adipogenic and osteogenic differentiation of hMSCs. In addition, both RGS2 and RGS4 play positive roles during adipogenesis but opposing roles during osteogenesis, with RGS2 as a positive regulator and RGS4 as a negative regulator. These results imply that members of RGS proteins may play multifaceted roles during human adipogenesis and osteogenesis to balance or counterbalance each other’s function during those processes. The online version of this article (10.1186/s40659-017-0148-1) contains supplementary material, which is available to authorized users.
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影响因子：
12.4
作者：
Chen Q;Shou P;Zheng C;Jiang M;Cao G;Yang Q;Cao J;Xie N;Velletri T;Zhang X;Xu C;Zhang L;Yang H;Hou J;Wang Y;Shi Y
通讯作者：
Shi Y
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
4.8
作者：
Ali, AA;Weinstein, RS;Jilka, RL
通讯作者：
Jilka, RL
影响因子：
5.3
作者：
Arvidson K;Abdallah BM;Applegate LA;Baldini N;Cenni E;Gomez-Barrena E;Granchi D;Kassem M;Konttinen YT;Mustafa K;Pioletti DP;Sillat T;Finne-Wistrand A
通讯作者：
Finne-Wistrand A
Osf2/Cbfa1：成骨细胞分化的转录激活因子
影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G