Magnesium ions facilitate integrin alpha 2- and alpha 3-mediated proliferation and enhance alkaline phosphatase expression and activity in hBMSCs

Abstract

Magnesium metal and its alloys have been proposed as a novel class of bone implant biomaterials because of their biodegradability and mechanical properties. The purpose of this study was to determine whether magnesium ions, which are released abundantly from alloys, affect proliferation and differentiation of human bone marrow-derived stromal cells (hBMSCs). High levels of magnesium ions did not induce cytotoxicity in hBMSCs, but treatment with 2.5-10 mm magnesium ions for 48-72 h significantly increased hBMSC proliferation. The expression of integrins α2 and α3, but not β1, was upregulated compared with the control and shifted from α3 to α2 in hBMSCs treated with magnesium ions. Knockdown of integrins α2 and/or α3 significantly reduced magnesium-induced proliferation of hBMSCs. Magnesium exposure profoundly enhanced alkaline phosphatase (ALP) gene expression and activity even at a relatively low magnesium concentration (2.5 mm). Exposure to magnesium ions facilitated hBMSC proliferation via integrin α2 and α3 expression and partly promoted differentiation into osteoblasts via the alteration of ALP expression and activity. Accordingly, magnesium could be a useful biomaterial for orthopaedic applications such as bone implant biomaterials for repair and regeneration of bone defects in orthopaedic and dental fields. Copyright © 2014 John Wiley & Sons, Ltd.

Behavior of bone cells in contact with magnesium implant material

“…That the results after a longer extract addition showed another picture leads to the assumption that extract and its ingredients induce initial osteoinduction. Also in human mesenchymal stem cells, an osteogenic effect in respect to gene expression was induced by higher Mg concentrations . In general, it has to be mentioned that it is difficult to distinguish singular effects of Mg‐ion concentration, pH, or osmolality.…”

“…Also in human mesenchymal stem cells, an osteogenic effect in respect to gene expression was induced by higher Mg concentrations. 34,35 In general, it has to be mentioned that it is difficult to distinguish singular effects of Mg-ion concentration, pH, or osmolality. However, in the authors' opinion, the effect is combinatorial, as with single salts or solely increasing the pH, these effects could not be observed.…”

A systemic study on key parameters affecting nanocomposite coatings on magnesium substrates

“…The nHA/PCL coated M_Mg showed the highest BMSC adhesion density among all the samples tested ( Figure 11, 14A), most likely because the synergy between Mg 2+ and nHA was beneficial for bone cell adhesion. It has been known that both Mg 2+ and nHA could increase bone cell adhesion [6,[85][86][87]. The non-coated Mg showed lower BMSC adhesion density and less spreading area per cell than the nHA/PCL coated Mg ( Figure 12A and 14B) because of the higher pH and unstable surface conditions caused by rapid degradation.…”

Magnesium release from mesoporous carriers on endosseus implants does not influence bone maturation at 6 weeks in rabbit bone.

“…12,16 Besides the introduction of foreign drugs or growth factors, with unknown long-term effects, mesoporous coatings may be used to increase the local content level of bioactive elements already present in the body, such as magnesium. The benefits of magnesium in bone healing range from incrementing the pre-osteoblast attachment to titanium surfaces, via an integrin-mediated pathway, 17,18 increasing the mesenchymal cell proliferation and differentiation toward the osteoblast lineage, 19 to the creation of hydroxyapatite crystals with enhanced mechanical properties. 17,20,21 On top of that magnesium is osteoconductive.…”