title: Tenascin-C mimetic Peptide nanofibers direct stem cell differentiation to osteogenic lineage.
abstract: Extracellular matrix contains various signals for cell surface receptors that regulate cell fate through modulation of cellular activities such as proliferation and differentiation. Cues from extracellular matrix components can be used for development of new materials to control the stem cell fate. In this study, we achieved control of stem cell fate toward osteogenic commitment by using a single extracellular matrix element despite the contradictory effect of mechanical stiffness. For this purpose, we mimicked bone extracellular matrix by incorporating functional sequence of fibronectin type III domain from native tenascin-C on self-assembled peptide nanofibers. When rat mesenchymal stem cells (rMSCs) were cultured on these peptide nanofibers, alkaline phosphatase (ALP) activity and alizarin red staining indicated osteogenic differentiation even in the absence of osteogenic supplements. Moreover, expression levels of osteogenic marker genes were significantly enhanced revealed by quantitative real-time polymerase chain reaction (qRT-PCR), which showed the remarkable bioactive role of this nanofiber system on osteogenic differentiation. Overall, these results showed that tenascin-C mimetic peptides significantly enhanced the attachment, proliferation, and osteogenic differentiation of rMSCs even in the absence of any external bioactive factors and regardless of the suitable stiff mechanical properties normally required for osteogenic differentiation. Thus, these peptide nanofibers provide a promising new platform for bone regeneration.
authors.affiliation: Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University , Ankara 06800, Turkey.
authors.forename: Melike
authors.initials: M
authors.lastname: Sever
authors.forename: Busra
authors.initials: B
authors.lastname: Mammadov
authors.forename: Mustafa O
authors.initials: MO
authors.lastname: Guler
authors.forename: Ayse B
authors.initials: AB
authors.lastname: Tekinay
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D017348:Microscopy, Electron, Scanning Transmission; D057139:Nanofibers / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012212:Rheology; D019063:Tenascin / Q000494:pharmacology*
chemical_list: D019063:Tenascin; D000469:Alkaline Phosphatase