Application of shear stress for enhanced osteogenic differentiation of mouse induced pluripotent stem cells

Author:

Limraksasin Phoonsuk,Nattasit Praphawi,Manokawinchoke Jeeranan,Tiskratok Watcharaphol,Vinaikosol Naruephorn,Okawa Hiroko,Limjeerajarus Chalida Nakalekha,Limjeerajarus Nuttapol,Pavasant Prasit,Osathanon Thanaphum,Egusa Hiroshi

Abstract

AbstractThe 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.

Funder

Japan Society for the Promotion of Science

the NSRF via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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