Mechanoresponsive MiR-138-5p Targets MACF1 to Inhibit Bone Formation

被引：1

作者：

Zhihao Chen ^{[1
,2
]}

Zhao Fan ^{[1
,2
]}

Liang Chao ^{[2
,3
]}

Lifang Hu ^{[1
,2
]}

Chen Lei ^{[1
,2
]}

Zhang Yan ^{[1
,2
]}

Yin Chong ^{[1
,2
]}

Dijie Li ^{[1
,2
]}

Tian Ye ^{[1
,2
]}

Wuxia Qiu ^{[1
,2
]}

Kewen Zhang ^{[1
,2
]}

Chaofei Yang ^{[1
,2
]}

Xiaona Li ^{[4
]}

Li Yu ^{[1
,2
]}

Weiyi Chen ^{[4
]}

Zhang Ge ^{[2
,3
]}

Qian Airong ^{[1
,2
]}

机构：

[1] Lab for Bone Metabolism,Key Lab for Space Biosciences and Biotechnology,Research Center for Special Medicine and Health Systems Engineering,NPU-UAB Joint Laboratory for Bone Metabolism,School of Life Sciences,Northwestern Polytechnical University

[2] Northwestern Polytechnical University-Hong Kong Baptist University Joint Rese arch Centre for Translational Medicine on Musculoskeletal Health in Space

[3] Institute for Advancing Translational Medicine in Bone and Joint Diseases,School of Chinese Medicine,Hong Kong Baptist University

[4] College of Biomedical Engineering,Taiyuan University of Technology

来源：

医用生物力学 | 2019年 / 34(S1)卷 / S1期

基金：

中国国家自然科学基金;

关键词：

Mechanoresponse; miR-138-5p; MACF1; bone formation;

D O I：

暂无

中图分类号：

R580 [];

学科分类号：

1002 ; 100201 ;

摘要：

Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies discover that bedridden patients showed osteoporotic T-scores and low bone mineral density,and long-term immobilized patients presented reduced markers of bone formation.However,as bone formation mediated by osteoblast differentiation is a complex process,the underlying molecular mechanism of mechanical stimuli regulating bone formation is still unclear.Recent evidences show that microRNAs(miRNAs)are involved in mechanical stimuli regulating bone formation or osteoblast differentiation.Nevertheless,no direct evidence identifies mechanoresponsive miRNA in both human and animal bones,and clarifies its mechanoresponsive role under different mechanical conditions(e.g.mechanical unloading,reloading,loading).In the current study,we screened for differentially expressed miRNAs in bone specimens of bedridden patients with fractures,then identified that the expression of miR-138-5p,but not the other miRNAs,altered withbedridden time and was negatively correlated with the expression of the bone formation marker genes Alp(alkaline phosphatase).Moreover,miR-138-5p was up-regulated with reduced bone formation during unloading and down-regulated with increased bone formation during reloading in hind4imb unloaded mice.In addition,miR-138-5p was verified to be responsive to different mechanical unloading condition and cyclic mechanical stretch condition in primary osteogenic cells,respectively.Further in vitro data suggested that mechanoresponsive miR-138-5p directly targeted microtubule actin crosslinking factor 1(MACF1)to inhibit osteoblast differentiation.In vivo,we constructed an osteoblastic miR-138-5p transgenic mice model(TG138)with the Runx2promoter,and found that overexpression miR-138-5p supressed bone formation.Moreover,osteoblast-targeted inhibition of miR-138-5p sensitized bone anabolic response to mechanical loading in TG138 mice.Predominantly,the osteoblast-targeted inhibition of miR-138-5p could counteract bone formation reduction induced by hind limb unloading.Taken together,the mechanoresponsive miR-138-5p inhibited bone anabolic response for developing a novel bone anabolic sensitization strategy.

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页码：72 / 73

页数：2