Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation.
Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation.
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DOI：
10.1038/s41467-021-27629-2
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发表时间：
2022-01-10
影响因子：
16.6
通讯作者：
Fan S
中科院分区：
文献类型：
--
作者：
Xie Z;Hou L;Shen S;Wu Y;Wang J;Jie Z;Zhao X;Li X;Zhang X;Chen J;Xu W;Ning L;Ma Q;Wang S;Wang H;Yuan P;Fang X;Qin A;Fan S
机械力对骨的发育和重建至关重要。在这里，我们报告，机械力调节生产的代谢产物不对称二甲基精氨酸（ADMA）通过调节水解酶二甲基精氨酸二甲氨基水解酶1（Ddah 1）在成骨细胞的表达。Ddah 1基因-394 4 N del/ins多态性和血清ADMA水平升高与骨密度呈负相关。Ddah 1的全局或成骨细胞特异性缺失导致ADMA水平增加，但骨形成减少。进一步的分子研究揭示了机械刺激增强TAZ/SMAD 4诱导的Ddah 1转录。Ddah 1在成骨细胞系细胞中的缺失未能对机械刺激相关的骨形成做出反应。总之，该研究揭示了机械力能够下调ADMA以增强骨形成。机械力对于骨骼的发育和重塑至关重要。在这里，作者报告说，机械力通过调节成骨细胞中水解酶二甲基精氨酸二甲氨基水解酶1的表达来调节代谢产物不对称二甲基精氨酸的产生。
Mechanical force is critical for the development and remodeling of bone. Here we report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine (ADMA) via regulating the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 (Ddah1) expression in osteoblasts. The presence of -394 4 N del/ins polymorphism of Ddah1 and higher serum ADMA concentration are negatively associated with bone mineral density. Global or osteoblast-specific deletion of Ddah1 leads to increased ADMA level but reduced bone formation. Further molecular study unveils that mechanical stimulation enhances TAZ/SMAD4-induced Ddah1 transcription. Deletion of Ddah1 in osteoblast-lineage cells fails to respond to mechanical stimulus-associated bone formation. Taken together, the study reveals mechanical force is capable of down-regulating ADMA to enhance bone formation. Mechanical force is critical for the development and remodeling of bones. Here the authors report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine via regulating the expression of the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 in osteoblasts.
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影响因子：
29
作者：
Fan W;Waizenegger W;Lin CS;Sorrentino V;He MX;Wall CE;Li H;Liddle C;Yu RT;Atkins AR;Auwerx J;Downes M;Evans RM
通讯作者：
Evans RM
影响因子：
3.9
作者：
Dowsett L;Higgins E;Alanazi S;Alshuwayer NA;Leiper FC;Leiper J
通讯作者：
Leiper J
影响因子：
16.2
作者：
Anderssohn, Maike;McLachlan, Stela;Price, Jackie F.
通讯作者：
Price, Jackie F.
影响因子：
5.2
作者：
Jannatbabaei, Atefeh;Tafazzoli-Shadpour, Mohammad;Seyedjafari, Ehsan
通讯作者：
Seyedjafari, Ehsan
DOI：
10.1161/atvbaha.110.222638
发表时间：
2011-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Hu X;Atzler D;Xu X;Zhang P;Guo H;Lu Z;Fassett J;Schwedhelm E;Böger RH;Bache RJ;Chen Y
通讯作者：
Chen Y