Role of bone morphogenetic protein-2 in osteogenic differentiation of mesenchymal stem cells

Abstract

Bone mesenchymal stem cells (BMSCs) have been an area of interest in biomedical research and tissue engineering due to their diverse differentiation abilities. In osteogenesis, bone morphogenetic proteins (BMPs), particularly BMP-2, are important. However, the effect of BMP-2 on the osteogenetic capacity of BMSCs remains to be fully elucidated. In the present study, primary rat BMSCs were infected with a recombinant lentivirus carrying the BMP-2 gene (Lenti-BMP-2), and the effects of BMP-2 on the activity of alkaline phosphatase (ALP) on days 3, 7, 14 and 21, and on mineralization on day 21 were evaluated. In addition, the adhesive ability of BMP-2-overexpressed BMSCs was detected using an adhesion assay. Following forced expression of BMP-2 in the BMSCs, the levels of osteogenic genes, including osteopontin (OPN), osteocalcin (OC) and collagen type I (Col-I), were detected and the nuclear accumulation of Runt-related transcription factor (Runx)-2 and phosphorylated small mothers against decapentaplegic (p-Smad) 1/5/8 was also evaluated. The results demonstrated that the rat BMSCs had been isolated, cultured and passaged from Sprague-Dawley rat bone marrow successfully, and the third-generation BMSCs were identified using flow cytometry with CD29 staining. The osteogenetic phenotype of the BMSCs, expressing ALP and osteocalcin, was significantly induced by BMP-2, and the proliferation of the BMSCs was enhanced by BMP-2. Furthermore, the adhesive potential of the BMP-2-overexpressed BMSCs was increased, the expression levels of OPN, OCN and Col-Ie osteogenetic factors were upregulated and the nuclear accumulation of Runx-2 and p-Smads1/5/8 were increased significantly. These data suggested that BMP-2 may facilitate the osteogenetic differentiation of rat BMSCs and provide a favorable cell resource for tissue engineering.

Dynamic expression of SMAD3 is critical in�osteoblast differentiation of PDMCs

“…The present study demon-demonstrated that, like osteoblasts derived from human mesenchymal stem cells (46,47), OM-treated PDMCs expressed BMP-2. BMPs are known to stimulate new bone formation (48).…”

“…BMPs are known to stimulate new bone formation (48). Sun et al (46) revealed that BMP-2 may improve bone healing in an animal model. Furthermore, the molecules RUNX2 and ALP, which are associated with osteoblast differentiation and bone activity, were also upregulated during the initial stages of differentiation (49)(50)(51).…”

Bone marrow-derived stem/stromal cells (BMSC) 3D microtissues cultured in BMP-2 supplemented osteogenic induction medium are prone to adipogenesis

“…While the influence of BMP-2 on BMSC differentiation has been studied extensively in 2D monolayers (Sun et al 2015), its effect on 3D microtissue cultures has been less well explored. As undifferentiated BMSC organised into 3D microtissues behave differently than those cultured in 2D monolayers (Wang et al 2009;Frith et al 2010;Kabiri et al 2012), we chose to characterise BMSC osteogenic induction in 3D microtissue cultures.…”

Modulation of human mesenchymal and pluripotent stem cell behavior using biophysical and biochemical cues: A review

“…For instance, in osteogenesis, these are generally ascorbate, b-glycerophosphate, and bone morphogenetic proteins (BMPs), or dexamethasone (DEX) (Cook and Genever, 2013). BMPs such as BMP-2 stimulate the expression of major osteogenic genes such as osteopontin, osteocalcin and Runx2 (Runt-related transcription factor 2) (Sun et al, 2015). Adipogenesis requires DEX, isobutylmethylxanthine, indomethacin, and insulin (Cook and Genever, 2013).…”