Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26558702
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Mechanosensitive TRPM7 mediates shear stress and modulates osteogenic
differentiation of mesenchymal stromal cells through Osterix pathway
#MMPMID26558702
Liu YS
; Liu YA
; Huang CJ
; Yen MH
; Tseng CT
; Chien S
; Lee OK
Sci Rep
2015[Nov]; 5
(?): 16522
PMID26558702
show ga
Microenvironments that modulate fate commitments of mesenchymal stromal cells
(MSCs) are composed of chemical and physical cues, but the latter ones are much
less investigated. Here we demonstrate that intermittent fluid shear stress
(IFSS), a potent and physiologically relevant mechanical stimulus, regulates
osteogenic differentiation of MSCs through Transient receptor potential
melastatin 7 (TRPM7)-Osterix axis. Immunostaining showed the localization of
TRPM7 near or at cell membrane upon IFSS, and calcium imaging analysis
demonstrated the transient increase of cytosolic free calcium. Expressions of
osteogenic marker genes including Osterix, but not Runx2, were upregulated after
three-hour IFSS. Phosphorylation of p38 and Smad1/5 was promoted by IFSS as well.
TRPM7 gene knockdown abolished the promotion of bone-related gene expressions and
phosphorylation. We illustrate that TRPM7 is mechanosensitive to shear force of
1.2 Pa, which is much lower than 98 Pa pressure loading reported recently, and
mediates distinct mechanotransduction pathways. Additionally, our results suggest
the differential roles of TRPM7 in endochondral and intramembranous ossification.
Together, this study elucidates the mechanotransduction in MSCs fate commitments
and displays an efficient mechano-modulation for MSCs osteogenic differentiation.
Such findings should be taken into consideration when designing relevant
scaffolds and microfluidic devices for osteogenic induction in the future.
free
free
free
