Chemical and genetic blockade of HDACs enhances osteogenic differentiation of human adipose tissue-derived stem cells by oppositely affecting osteogenic and adipogenic transcription factors

There is a current clinical need for the development of bone void fillers and bioactive bone graft substitutes. The use of mesenchymal stem cells (MSCs) that are seeded into 3D scaffolds and induce bone generation in the event of MSCs osteogenic differentiation is highly promising. Since calcium ions and phosphates promote the osteogenic differentiation of MSCs, the use of the calcium complexes of phosphate-containing polymers is highly prospective in the development of osteogenic scaffolds. Calcium poly(ethylene phosphate)s (PEP-Ca) appear to be potentially suitable candidates primarily because of PEP’s biodegradability. In a series of experiments with human adipose-tissue-derived multipotent mesenchymal stem cells (ADSCs), we demonstrated that PEP-Ca are non-toxic and give rise to osteogenesis gene marker, bone morphogenetic protein 2 (BMP-2) and mineralization of the intercellular matrix. Owing to the synthetic availability of poly(ethylene phosphoric acid) block copolymers, these results hold out the possibility for the development of promising new polymer composites for orthopaedic and maxillofacial surgery.

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Effect of MicroRNA-20a on Osteogenic Differentiation of Human Adipose Tissue-Derived Stem Cells

Cells Tissues Organs ◽

10.1159/000506304 ◽

2019 ◽

Vol 208 (3-4) ◽

pp. 148-157

Author(s):

Tao Luo ◽

Xueqin Yang ◽

Yan Sun ◽

Xinqi Huang ◽

Ling Zou ◽

...

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Osteogenic Differentiation ◽

Fluorescent Protein ◽

Mrna Level ◽

Human Adipose Tissue ◽

Associated Proteins ◽

Green Fluorescent

Osteogenic differentiation of human adipose tissue-derived stem cells (hASCs) is a complex process that is regulated by multiple factors, including microRNAs (miRNAs). The miRNA miR-20a was shown to promote bone formation from bone marrow-derived mesenchymal stem cells. However, the role of miR-20a in osteogenic differentiation of hASCs remains unclear. In this study, we systematically evaluated the function of miR-20a in regulating hASC osteogenesis in vitro. hASCs were transduced with miR-20a-overexpressing and miR-20a-sponge lentiviral vectors, with green fluorescent protein (GFP) as a control. The results showed that miR-20a transcription was upregulated after hASC mineralization. Compared with the miR-20a-sponge, GFP, and hASC groups, the miR-20a-overexpressing group showed higher alkaline phosphatase (ALP) activity on days 7 and 14. Moreover, the mRNA level of ALP increased significantly in the miR-20a-overexpressing group on day 14. Furthermore, the protein of the target gene PPARγ was decreased, and the osteogenic differentiation-associated proteins ALP, osteocalcin, and RUNX2 were upregulated. hASCs anchored to HA/β-TCP revealed a healthy polygonal morphology and developed cytoplasmic extensions. miR-20a promoted osteogenic differentiation of the cell scaffold. Taken together, these data confirm that miRNA-20a promotes the osteogenesis of hASCs in vitro, and its essential role in vivo needs further investigation.

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