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Bone Morphogenetic Protein-2 Accelerates Osteogenic Differentiation in Spheroid-Derived Mesenchymal Stem Cells
| Content Provider | Semantic Scholar |
|---|---|
| Author | Miyaguchi, Naoyuki Kajiya, Hiroshi Yamaguchi, Masahiro Sato, Ayako Yasunaga, Madoka Toshimitu, Takuya Yanagi, Tsukasa Matsumoto, Ayako Kido, Hirofumi Ohno, Jun |
| Copyright Year | 2018 |
| Abstract | Introduction Adult mesenchymal stem cells (MSCs) are found in pulp, cord blood, umbilical cord and others. MSCs possess great potential for tissue engineering and regenerative medicine, because of their capability of self-renewal and multilineage differentiation. MSCs have been utilized as a cell source for osteogenic tissue regeneration because culture in the presence of osteogenic supplements facilitates MSCs to undergo differentiation into the osteogenic phenotypes . Osteogenic differentiation is regulated by various signaling pathways, including Wnt, bone morphogenetic protein (BMP), Hedgehog, Notch, and fibroblast growth factors. BMPs, members of the transforming growth factor-β (TGFβ) superfamily, regulate proliferation, differentiation, and apoptosis in various types of cells and organs in embryonic development and postnatal physiological function. When BMPscontaining scaffolds are implanted into rodent tissues, ectopic bone formation is induced by BMPs. BMPs, including BMP-2 and -4, accelerate osteoblast differentiation of MSCs via activation of transcription factors, such as Runx2/core binding factor a1 (Cbfa1) and Sp7/osterix . In addition, Smad proteins play an important role in the intracellular signaling of BMPs in mammals. Receptor-activated Smad (R-Smad) proteins, Smad1, Smad2, Smad3, Smad5, and Smad8, are directly phosphorylated by type I TGF-β receptors. Upon activation, R-Smad form complexes with the Co-Smad, Smad4, and translocate to the nucleus to regulate gene expression by binding to regulatory regions of the target genes. Although relatively easy and traditional, 2D culture is an artificial and less physiologically relevant environment, because in vivo characteristics and traits are lost or compromised. Furthermore, in conventional 2D in vitro monolayer culture techniques, MSCs eventually lose intrinsic properties, such as self-renewal, replication, colony-forming efficiency, and differentiation capacity. Spheroid 3D environments are generally considered more favorable than 2D monolayer culture. Various culture systems have recently been developed to generate 3D multicellular spheroids from MSCs, such as suspension, hanging drop, micropattern substrates, and non-adherent surfaces. In 3D-cultured spheroids, self-renewal has been reported to be significantly enhanced . Additionally, MSC spheroids formed on micropattern substrates and non-adherent surfaces have higher osteogenic and adipogenic differentiation efficiencies . In this study, we employed a low-attachment culture condition to generate MSC spheroids. The osteogenic properties of spheroid-derived MSCs were investigated. We further examined an effect of BMP-2 on acceleration of osteogenesis in spheroid-derived Journal of Hard Tissue Biology 27[4] (2018) 343-35 |
| Starting Page | 343 |
| Ending Page | 350 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| DOI | 10.2485/jhtb.27.343 |
| Volume Number | 27 |
| Alternate Webpage(s) | https://www.jstage.jst.go.jp/article/jhtb/27/4/27_343/_pdf |
| Alternate Webpage(s) | https://doi.org/10.2485/jhtb.27.343 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
