TY - JOUR
T1 - Application of shear stress for enhanced osteogenic differentiation of mouse induced pluripotent stem cells
AU - Limraksasin, Phoonsuk
AU - Nattasit, Praphawi
AU - Manokawinchoke, Jeeranan
AU - Tiskratok, Watcharaphol
AU - Vinaikosol, Naruephorn
AU - Okawa, Hiroko
AU - Limjeerajarus, Chalida Nakalekha
AU - Limjeerajarus, Nuttapol
AU - Pavasant, Prasit
AU - Osathanon, Thanaphum
AU - Egusa, Hiroshi
N1 - Funding Information:
This work was supported by Grant-in-Aid for Young Scientists (JP21K17005, P.L.) from the Japan Society for the Promotion of Science. This study was also supported by the NSRF via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation (B16F640118, T.O., P.P., and H.E.).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The self-organizing potential of induced pluripotent stem cells (iPSCs) represents a promising tool for bone tissue engineering. Shear stress promotes the osteogenic differentiation of mesenchymal stem cells, leading us to hypothesize that specific shear stress could enhance the osteogenic differentiation of iPSCs. For osteogenesis, embryoid bodies were formed for two days and then maintained in medium supplemented with retinoic acid for three days, followed by adherent culture in osteogenic induction medium for one day. The cells were then subjected to shear loading (0.15, 0.5, or 1.5 Pa) for two days. Among different magnitudes tested, 0.5 Pa induced the highest levels of osteogenic gene expression and greatest mineral deposition, corresponding to upregulated connexin 43 (Cx43) and phosphorylated Erk1/2 expression. Erk1/2 inhibition during shear loading resulted in decreased osteogenic gene expression and the suppression of mineral deposition. These results suggest that shear stress (0.5 Pa) enhances the osteogenic differentiation of iPSCs, partly through Cx43 and Erk1/2 signaling. Our findings shed light on the application of shear-stress technology to improve iPSC-based tissue-engineered bone for regenerative bone therapy.
AB - The self-organizing potential of induced pluripotent stem cells (iPSCs) represents a promising tool for bone tissue engineering. Shear stress promotes the osteogenic differentiation of mesenchymal stem cells, leading us to hypothesize that specific shear stress could enhance the osteogenic differentiation of iPSCs. For osteogenesis, embryoid bodies were formed for two days and then maintained in medium supplemented with retinoic acid for three days, followed by adherent culture in osteogenic induction medium for one day. The cells were then subjected to shear loading (0.15, 0.5, or 1.5 Pa) for two days. Among different magnitudes tested, 0.5 Pa induced the highest levels of osteogenic gene expression and greatest mineral deposition, corresponding to upregulated connexin 43 (Cx43) and phosphorylated Erk1/2 expression. Erk1/2 inhibition during shear loading resulted in decreased osteogenic gene expression and the suppression of mineral deposition. These results suggest that shear stress (0.5 Pa) enhances the osteogenic differentiation of iPSCs, partly through Cx43 and Erk1/2 signaling. Our findings shed light on the application of shear-stress technology to improve iPSC-based tissue-engineered bone for regenerative bone therapy.
UR - http://www.scopus.com/inward/record.url?scp=85141550029&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85141550029&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-21479-8
DO - 10.1038/s41598-022-21479-8
M3 - Article
C2 - 36347883
AN - SCOPUS:85141550029
VL - 12
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 19021
ER -