Abstract
Mechanical stimulation is an important factor regulating mesenchymal stem cell (MSC) functions such as proliferation. The Ca2+‐activated K+ channel, KCa3.1, is critically engaged in MSC proliferation but its role in mechanical regulation of MSC proliferation remains unknown. Here, we examined the KCa3.1 channel expression and its role in rat bone marrow‐derived MSC (BMSC) proliferation in response to mechanical stretch. Application of mechanical stretch stimulated BMSC proliferation via promoting cell cycle progression. Such mechanical stimulation up‐regulated the KCa3.1 channel expression and pharmacological or genetic inhibition of the KCa3.1 channel strongly suppressed stretch‐induced increase in cell proliferation and cell cycle progression. These results support that the KCa3.1 channel plays an important role in transducing mechanical forces to MSC proliferation. Our finding provides new mechanistic insights into how mechanical stimuli regulate MSC proliferation and also a viable bioengineering approach to improve MSC proliferation.
Highlights
Mesenchymal stem cells (MSCs) have many promising applications in regenerative medicine.[1,2] The capability of mesenchymal stem cell (MSC) proliferation declines upon in vitro expansion.[3,4] Identification of practical methods to maintain or increase MSC proliferation to increase their availability is helpful to their clinical applications
Previous studies showed that the expression of the KCa3.1 channel in human umbilical vein endothelium cells was up-regulated by fluid flow-induced shear stress, or its channel activity in vascular smooth muscle cells was enhanced by hypotonic solution-induced membrane stretch.[12,13]
We investigated whether the KCa3.1 channel plays a role in mechanical stretch-induced stimulation of bone marrow-derived MSC (BMSC) proliferation
Summary
Mesenchymal stem cells (MSCs) have many promising applications in regenerative medicine.[1,2] The capability of MSC proliferation declines upon in vitro expansion.[3,4] Identification of practical methods to maintain or increase MSC proliferation to increase their availability is helpful to their clinical applications. We showed that application of mechanical stretch to rat bone marrow-derived MSCs (BMSCs) significantly increased cell proliferation, mainly via altering cell cycle progression. Such mechanical stretch up-regulated the KCa3.1 expression at mRNA, protein and functional levels. Mechanical stretch-induced stimulation of BMSC proliferation and alteration in cell cycle progression were prevented by pharmacological inhibition of the KCa3.1 channel or siRNA-mediated knockdown of the KCa3.1 expression. Our results provide compelling evidence to support an important role of the KCa3.1 channel in mechanical stimuli-induced stimulation of MSC proliferation, revealing a new molecular mechanism in transducing mechanical forces to regulate MSC proliferation and identifying a viable bioengineering approach to improve MSC proliferation
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