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β-Catenin Limits Osteogenesis on Regenerative Materials in a Stiffness-Dependent Manner.
- Source :
-
Advanced healthcare materials [Adv Healthc Mater] 2021 Dec; Vol. 10 (23), pp. e2101467. Date of Electronic Publication: 2021 Oct 08. - Publication Year :
- 2021
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Abstract
- Targeted refinement of regenerative materials requires mechanistic understanding of cell-material interactions. The nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffold is shown to promote skull regeneration in vivo without additive exogenous growth factors or progenitor cells, suggesting potential for clinical translation. This work evaluates modulation of MC-GAG stiffness on canonical Wnt (cWnt) signaling. Primary human bone marrow-derived mesenchymal stem cells (hMSCs) are differentiated on two MC-GAG scaffolds (noncrosslinked, NX-MC, 0.3 kPa vs conventionally crosslinked, MC, 3.9 kPa). hMSCs increase expression of activated β-catenin, the major cWnt intracellular mediator, and the mechanosensitive YAP protein with near complete subcellular colocalization on stiffer MC scaffolds. Overall Wnt pathway inhibition reduces activated β-catenin and osteogenic differentiation, while elevating BMP4 and phosphorylated Smad1/5 (p-Smad1/5) expression on MC, but not NX-MC. Unlike Wnt pathway downregulation, isolated canonical Wnt inhibition with β-catenin knockdown increases osteogenic differentiation and mineralization specifically on the stiffer MC. β-catenin knockdown also increases p-Smad1/5, Runx2, and BMP4 expression only on the stiffer MC material. Thus, while stiffness-induced activation of the Wnt and mechanotransduction pathways promotes osteogenesis on MC-GAG, activated β-catenin is a limiting agent and may serve as a useful target or readout for optimal modulation of stiffness in skeletal regenerative materials.<br /> (© 2021 Wiley-VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 2192-2659
- Volume :
- 10
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Advanced healthcare materials
- Publication Type :
- Academic Journal
- Accession number :
- 34585526
- Full Text :
- https://doi.org/10.1002/adhm.202101467