Primary cilia/intraflagellar transport mediates mechanics-responsive signaling pathway and promotes osteogenic differentiation of bone marrow stromal stem cells
- VernacularTitle:初级纤毛/鞭毛转运系统介导力学反应性信号通路促骨髓基质干细胞成骨分化
- Author:
Zhanhua MA
1
;
Xu YAN
;
Yan JIANG
;
Zhengming CAO
;
Yongkui WANG
;
Dongzhe LI
;
Tengyue YANG
;
Yikai JIN
;
Su FU
;
Chunlin ZHANG
Author Information
- Keywords: bone marrow stromal stem cell; transforming growth factor β1; bone morphogenetic protein 2; primary cilia; intraflagellar transport; shear stress stimulation
- From: Chinese Journal of Tissue Engineering Research 2024;28(25):3937-3941
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Mechanical stimulation has been confirmed to promote osteogenic differentiation of bone marrow stromal stem cells,but the mechanism is unknown.Primary cilia are important mechanoreceptors and regulate various signaling pathways such as TGF-β1/BMP-2/SMAD.They are likely to be important targets for mechanical regulation of bone marrow stromal stem cells. OBJECTIVE:To investigate the effect and mechanism of fluid shear stress on osteogenic differentiation of bone marrow stromal stem cells. METHODS:Rat bone marrow stromal stem cells were divided into control group,mechanical stimulation group(fluid shear mechanics intervention by shaking table),mechanical stimulation + IFT88 silencing group(mechanical stimulation + silencing IFT88 expression with siRNA).After 24 hours of intervention,qRT-PCR was utilized to determine the expression of transforming growth factor β1 and bone morphogenetic protein 2.Western blot assay was used to detect the expression of phosphorylated SMAD2/3 protein.Immunofluorescent staining of primary cilia was conducted and morphology was analyzed. RESULTS AND CONCLUSION:Shear stress stimulation could promote the transcriptional activity of transforming growth factor β1 and bone morphogenetic protein 2 genes,and increase the expression of phosphorylated SMAD2/3 protein.After siRNA interfered with primary cilia,this mechanical response effect was significantly reduced.There was a Spearman correlation between the change ratio of the primary cilium area of bone marrow stromal stem cells and the increased ratio of transforming growth factor β1 and bone morphogenetic protein 2 gene transcription.These findings indicate that primary cilia/intraflagellar transport mediates the activation of fluid shear stress-responsive transforming growth factor β1/bone morphogenetic protein 2/SMAD signaling pathway and promotes osteogenic differentiation of bone marrow stromal stem cells.
