title: Extracellular calcium and CaSR drive osteoinduction in mesenchymal stromal cells.
abstract: Bone is the main store of calcium and progenitor cells in the body. During the resorption process, the local calcium concentration reaches 8-40mM, 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 ([Ca(2+)]o) and the CaSR in osteoinduction. Rat bone marrow mesenchymal stromal cells (rBMSCs) were stimulated with 10mM of Ca(2+). Several experiments were conducted to demonstrate the effect of [Ca(2+)]o on chemotaxis, proliferation and differentiation on the osteoblastic lineage. It was found that [Ca(2+)]o induces rBMSCs to migrate and proliferate in a concentration-dependent manner. Real-time polymerase chain reaction and immunofluorescence also revealed that 10mM Ca(2+) 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 Ca(2+). Moreover, CaSR blockage inhibited the cellular response to stimulation with high concentrations of [Ca(2+)]o, revealing that the CaSR is a key modulator of these cellular responses.
authors: Biomaterials for Regenerative Therapies Group, Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, Barcelona 08028, Spain; CIBER-BBN, María de Luna 11, Zaragoza 50118, Spain.
authors: Arlyng
authors: A
authors: González-Vázquez
authors: Biomaterials for Regenerative Therapies Group, Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, Barcelona 08028, Spain; CIBER-BBN, María de Luna 11, Zaragoza 50118, Spain.
authors: Josep A
authors: JA
authors: Planell
authors: Biomaterials for Regenerative Therapies Group, Institute for Bioengineering of Catalonia, Baldiri Reixac 15-21, Barcelona 08028, Spain; Technical University of Catalonia, Av. Diagonal 647, Barcelona 08028, Spain; CIBER-BBN, María de Luna 11, Zaragoza 50118, Spain. Electronic address: eengel@ibecbarcelona.eu.
authors: Elisabeth
authors: E
authors: Engel
mesh_terms: D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D017931:DNA Primers; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D044169:Receptors, Calcium-Sensing; D002118:Calcium
keywords: Calcium sensing receptor (CaSR); Extracellular calcium; Mesenchymal stromal cells (MSCs); Osteoinduction; Regenerative medicine