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Extracellular calcium and CaSR drive osteoinduction in mesenchymal stromal cells
Gonzalez Vazquez, Arlyng; Planell Estany, Josep Anton; Engel López, Elisabeth
Universitat Politècnica de Catalunya. Departament de Ciència dels Materials i Enginyeria Metal·lúrgica; Institut de Bioenginyeria de Catalunya; Universitat Politècnica de Catalunya. BBT - Biomaterials, Biomecànica i Enginyeria de Teixits
Bone is the main store of calcium and progenitor cells in the body. During the resorption process, the local calcium concentration reaches 8-40 mM, and the surrounding cells are exposed to these fluctuations in calcium. This stimulus is a signal that is detected through the calcium sensing receptor (CaSR), which modulates chemotactic and proliferative G protein-dependent signaling pathways. The objective of the present work is to evaluate the roles of extracellular calcium ([Ca2+](o)) and the CaSR in osteoinduction. Rat bone marrow mesenchymal stromal cells (rBMSCs) were stimulated with 10 mM of Ca2+. Several experiments were conducted to demonstrate the effect of [Ca2+](o) on chemotaxis, proliferation and differentiation on the osteoblastic lineage. It was found that [Ca2+](o) induces rBMSCs to migrate and proliferate in a concentration-dependent manner. Real-time polymerase chain reaction and immunofluorescence also revealed that 10 mM Ca2+ stimulates overexpression of osteogenic markers in rBMSCs, including alkaline phosphatase (ALP), bone sialoprotein, collagen Ia1 and osteocalcin. Functional assays determining ALP activity and mineralization tests both corroborate the increased expression of these markers in rBMSCs stimulated with Ca2+. Moreover, CaSR blockage inhibited the cellular response to stimulation with high concentrations of [Ca2+](o), revealing that the CaSR is a key modulator of these cellular responses. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Peer Reviewed
-Àrees temàtiques de la UPC::Enginyeria dels materials
-Regenerative medicine
-Calcium--Receptors
-Calcium sensing receptor (CaSR)
-Extracellular calcium
-Mesenchymal stromal cells (MSCs)
-Osteoinduction
-Regenerative medicine
-SENSING-RECEPTOR
-BONE-MARROW
-STEM-CELLS
-IN-VITRO
-OSTEOBLAST FUNCTION
-MC3T3-E1 CELLS
-DIFFERENTIATION
-PROLIFERATION
-EXPRESSION
-TISSUE
-Medicina regenerativa
-Calci
Attribution-NonCommercial-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
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