Magnesium Is a Key Regulator of the Balance between Osteoclast and Osteoblast Differentiation in the Presence of Vitamin D3

Abstract

Magnesium (Mg) is crucial for bone health. Low concentrations of Mg inhibit the activity of osteoblasts while promoting that of osteoclasts, with the final result of inducing osteopenia. Conversely, little is known about the effects of high concentrations of extracellular Mg on osteoclasts and osteoblasts. Since the differentiation and activation of these cells is coordinated by vitamin D3 (VD3), we investigated the effects of high extracellular Mg, as well as its impact on VD3 activity, in these cells. U937 cells were induced to osteoclastic differentiation by VD3 in the presence of supra-physiological concentrations (>1 mM) of extracellular Mg. The effect of high Mg concentrations was also studied in human bone-marrow-derived mesenchymal stem cells (bMSCs) induced to differentiate into osteoblasts by VD3. We demonstrate that high extra-cellular Mg levels potentiate VD3-induced osteoclastic differentiation, while decreasing osteoblastogenesis. We hypothesize that Mg might reprogram VD3 activity on bone remodeling, causing an unbalanced activation of osteoclasts and osteoblasts.

Osteoclast and osteoblast responsive carbonate apatite coatings for biodegradable magnesium alloys

“…As a result, the cell detachment was enhanced with an increase of the carbonate content rate. Since the osteoclast behavior depended on the concentration of Mg ions, pH and coexisting substances which varied depending on the corrosion speed of and the distance from the implanted Mg materials [23][24][25], further examination is necessary to understand the entire degradation of the CAp-coated Mg alloy accompanying osteoclastic resorption. Differentiation of precursor cells to multinucleated osteoclasts was enhanced by the CAp and HAp coatings comparing to that on the glass as revealed by the larger number of multinucleated cells on the CAp and Hap coatings than that on the glass shown in Figures 4, 5, S1 and S2.…”

“…One thing to be concerned is that osteoclastic activity may be decreased on Mg alloy surface because alkaline environments and Mg ions suppressed osteoclastic activities [22] and the number of osteoclasts in peri-implant tissue decreased around the Mg(OH) 2 cylinder implanted in rabbit femur [23]. The effect of Mg ions on osteoclasts and osteoblasts depended on the concentration of Mg ions and the coexisting substances like receptor activator of NF-κB ligand (RANKL) and vitamin D 3 [24,25].…”

A Review of the Action of Magnesium on Several Processes Involved in the Modulation of Hematopoiesis

“…In the last few decades, several studies pointed indirectly to this when they related the importance of Mg 2+ for cell-cycle progress, cell differentiation, apoptosis, the balance between osteoblast and adipocytes, etc. [ 3 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. In light of the above, our objective in this review is to discuss how changes in Mg 2+ homeostasis could influence bone marrow and, consequently, the hematopoiesis process, and what mechanisms may be involved.…”

Analysis of Intracellular Magnesium and Mineral Depositions during Osteogenic Commitment of 3D Cultured Saos2 Cells

“…The involvement of magnesium in osteogenic differentiation is rather puzzling, mainly due to its complex and multifactorial role in cell metabolism. More and more evidences suggest that magnesium acts primarily as a signaling element in cell metabolism and the concept that Mg is an electrolyte is too simplistic and obsolete [8,[26][27][28][29][30].…”

“…Fundamental differences exist between various cell types in the contribution of Mg to cell differentiation. Mg restriction retards cell differentiation of U937 cells towards osteoclasts, while mesenchymal cells differentiation toward pre-adipocytes seems to be independent from extracellular Mg [8]. Furthermore, Mg deficiency reversibly antagonizes the differentiation of promyelocytic leukemia HL60 cells exposed to differentiating agents such as DMSO and retinoic acid [9].…”