Diverse effect of BMP-2 homodimer on mesenchymal progenitors of different origin

Abstract

Bone morphogenetic protein-2 (BMP-2), is a potential factor to enhance osseointegration of dental implants. However, the appropriate cellular system to investigate the osteogenic effect of BMP-2 in vitro in a standardized manner still needs to be defined. The aim of this study was to examine the effect of BMP-2 on the cell proliferation and osteogenic differentiation of human osteogenic progenitors of various origins: dental pulp stem cells (DPSC), human osteosarcoma cell line (Saos-2) and human embryonic palatal mesenchymal cell line (HEPM). For induction of osteogenic differentiation, cell culture medium was supplemented with BMP-2 homodimer alone or in combination with conventionally used differentiation inducing agents. Differentiation was monitored for 6–18 days. To assess differentiation, proliferation rate, alkaline phosphatase activity, calcium deposition and the expression level of osteogenic differentiation marker genes (Runx2, BMP-2) were measured. BMP-2 inhibited cell proliferation in a concentration and time-dependent manner. In a concentration which caused maximal cell proliferation, BMP-2 did not induce osteogenic differentiation in any of the tested systems. However, it had a synergistic effect with the osteoinductive medium in both DPSC and Saos-2, but not in HEPM cells. We also found that the differentiation process was faster in Saos-2 than in DPSCs. Osteogenic differentiation could not be induced in the osteoblast progenitor HEPM cells. Our data suggest that in a concentration that inhibits proliferation the differentiation inducing effect of BMP-2 is evident only in the presence of permissive osteoinductive components. β-glycerophosphate, was identified interacting with BMP-2 in a synergistic manner.

Gene Expression Regulation and Secretory Activity of Mesenchymal Stem Cells upon In Vitro Contact with Microarc Calcium Phosphate Coating

“…Ca 2+ and Pi upregulate the expression of OCN, Runx2 and BMP-2 [ 30 ]. Pi can initiate signaling via extracellular signal-regulated kinases (ERK) and cAMP/protein kinase pathways, and activation of these signaling pathways increases BMP-2 expression [ 37 ].…”

“…Ca 2+ ions formed during degradation of biomaterials are inducers of ALP expression [ 35 ] and the differentiation of MSCs into osteoblasts is triggered through the expression of calcium-binding proteins [ 39 ]. In turn, an increase in the level of ALPL gene mRNA expression ensures the presence of free Pi in the cellular microenvironment, and this Pi binds with calcium to form CaP minerals in the bone [ 37 ].…”

Formulation, Colloidal Characterization, and In Vitro Biological Effect of BMP-2 Loaded PLGA Nanoparticles for Bone Regeneration

“…However, this property must be balanced with both migration and differentiation, and not all three characteristics increase at the same time and with the same ratios [55]. In fact, reportedly, when a dose of BMP-2 induces higher proliferation, it decreases differentiation [56]. This property has been extensively analyzed but discrepancies can still be detected in the literature.…”

“…It has been confirmed that cell differentiation induced by BMP-2 needs the presence of permissive osteoinductive components. Particularly, β-glycerophosphate has been shown to exert a synergistic effect with BMP-2 in inducing cell differentiation [56]. Thus, to test for osteogenic differentiation, we analyzed the expression of ALP mRNA.…”

Bioenergetic Impairment of Triethylene Glycol Dimethacrylate- (TEGDMA-) Treated Dental Pulp Stem Cells (DPSCs) and Isolated Brain Mitochondria are Amended by Redox Compound Methylene Blue

“…DPSCs play a crucial biological role in dental regenerative capacity [18][19][20][21], exhibit mesenchymal stem cell characteristics and serve to renew the dentin and the pulp following damage [22][23][24]. They also have marked anti-inflammatory effects, thereby counteracting local inflammation [25].…”