Molecular and genetic regulation of osteogenic differentiation of mesenchymal stromal cells

Kozhevnikova, M. N.; Mikaelyan, Arsen; Старостин, В. И.

doi:10.1134/s1062359008030011

Cited by 14 publications

(12 citation statements)

References 70 publications

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“…gao et al profiles of gene Runx2, which is associated with the initiation of osteoblast differentiation, 31 and Col1a1, which is involved in the biosynthesis of ECM, correlated well with the change in OCN, and Western blot analysis appeared to support this result at protein level ( Figure 4E). …”

supporting

confidence: 55%

Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

Gao¹,

Zhang²,

Song³

et al. 2015

IJN

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The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL) nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA) was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than cells on randomly oriented nanofibers. Furthermore, the aligned nanofibers with osteoinductive peptides could direct osteogenic differentiation of human mesenchymal stem cells even in the absence of osteoinducting factors, suggesting superior osteogenic efficacy of biomimetic design that combines the advantages of osteoinductive peptide signal and highly ordered nanofibers on cell fate decision. The presented peptide-decorated bone-mimic nanofiber scaffolds hold a promising potential in the context of bone tissue engineering.

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supporting

confidence: 55%

Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

Gao¹,

Zhang²,

Song³

et al. 2015

IJN

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“…4,43 Runx2 is one of the earliest and most specific regulators of osteoblast differentiation. [44][45][46] We found that Runx2 is activated by BMP-2 within the first day, by BMP-9 and pBMP-9 from day 3, and by pBMP-9 (400 ng=mL) only by day 6. Thus, pBMP-9, like the entire BMP-9, can trigger the expression of the transcription FIG.…”

Section: Discussionmentioning

confidence: 94%

Murine Preosteoblast Differentiation Induced by a Peptide Derived from Bone Morphogenetic Proteins-9

Bergeron

Senta²,

Mailloux³

et al. 2009

Tissue Engineering Part A

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Bone morphogenetic proteins (BMPs) increase the differentiation of osteoblasts implicated in bone formation and repair. In a previous study, we demonstrated that a peptide derived from BMP-9 (pBMP-9) at 400 ng/mL inhibited murine preosteoblasts MC3T3-E1 proliferation. Here, we compared the effects of equimolar concentrations of BMP-2 (50 ng/mL), BMP-9 (42.3 ng/mL), and pBMP-9 (4.52 ng/mL) on the differentiation of MC3T3-E1 in a serum-free medium. Like BMP-2, BMP-9 and pBMP-9 activated the Smad pathway. In contrary to BMP-2, the Smad phosphorylation induced by BMP-9 and pBMP-9 is not prevented by noggin, an extracellular antagonist of BMP-2. Further, BMP-9 and pBMP-9 increased, dose dependently, alkaline phosphatase activity, an early marker of osteoblast differentiation, after 1 day. Quantitative real-time polymerase chain reaction analysis demonstrated that BMP-2, BMP-9, and pBMP-9 (4.52 or 400 ng/mL) all activated the transcription of Runx2, Osterix, type I collagen alpha1 chain, and Osteocalcin genes within day 6. Alizarin red S quantification demonstrated that pBMP-9 (400 ng/mL) and pBMP-9 (4.52 ng/mL) allowed a slight deposition of Ca(2+) in the extracellular matrix of cells within 12 and 18 days, respectively. Therefore, pBMP-9 might be a promising replacement for costly BMP in tissue engineering applications that require a well-defined serum-free medium.

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“…A subset of genes was classified into the following functional categories relevant to the present study: bone mineralization, ossification, BMP receptor signaling, stem cell differentiation, osteoblast differentiation, osteoblast development, and extra cellular matrix molecules (particularly collagen molecules) and compared the fold expression change on both the surfaces (Table 1). Although collagen type 1 is the major component of the bone and is generally associated with ECM biosynthesis [34, 44, 45], other collagen genes that were up- or downregulated after 14 days of culture were analyzed and listed in Table 1. Most of them showed similar expression profiles on both substrates.…”

Section: Resultsmentioning

confidence: 99%

Regulation of osteogenic differentiation of rat bone marrow stromal cells on 2D nanorod substrates

et al. 2010

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Bone marrow stromal cells (BMSCs) possess multi-lineage differentiation potential and can be induced to undergo differentiation into various cell types with the correct combination of chemical and environmental factors. Although, they have shown great prospects in therapeutic and medical applications, less is known about their behavior on nanosurfaces mimicking the extra cellular matrix (ECM). In this report we have employed 2D substrates coated with tobacco mosaic virus (TMV) nanorods to study the differentiation process of BMSCs into osteoblast-like cells. TMV is a rod-shaped plant virus with an average length of 300 nm and diameter of 18 nm. The osteogenic differentiation of BMSCs on TMV was studied over time points of 7, 14 and 21 days. We examined the temporal gene expression changes during these time points by real time quantitative PCR (RT-qPCR) analysis. As expected, osteo-specific genes (osteocalcin, osteopontin and osteonectin) were upregulated and showed a maximum change in expression on TMV at 14 days which was 7 days earlier than on tissue culture plastic (TCP). Based on the genes expression profile generated by RT-qPCR experiments, we proposed that the early interaction of cells with TMV triggers on signaling pathways which regulate speedy expression of osteocalcin in turn, resulting in early mineralization of the cells. To further investigate these regulating factors we studied global changes in gene expression (DNA microarray analyses) during osteogenic differentiation on the nanosubstrate. Multitudes of genes were affected by culturing cells on nanorod substrate, which corroborated our initial PCR findings. Microarray analysis further revealed additional targets influenced by the presence of nanorods on the surface, of which, the expression of bone morphogenetic protein 2 (BMP2) was of particular interests. Further investigation into the temporal change of BMP2, revealed that it acts as a major promoter in signaling the early regulation of osteocalcin on TMV coated substrates.

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Molecular and genetic regulation of osteogenic differentiation of mesenchymal stromal cells

Cited by 14 publications

References 70 publications

Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

Murine Preosteoblast Differentiation Induced by a Peptide Derived from Bone Morphogenetic Proteins-9

Regulation of osteogenic differentiation of rat bone marrow stromal cells on 2D nanorod substrates

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