title: High extracellular magnesium inhibits mineralized matrix deposition and modulates intracellular calcium signaling in human bone marrow-derived mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) have the potential to differentiate into several cell types and provide an attractive source of autologous cells for regenerative medicine. However, their cellular biology is not fully understood. Similar to Ca(2+), extracellular Mg(2+) plays an important role in the functions of the skeletal system. Here, we examined the effects of extracellular Mg(2+) on the deposition of calcium phosphate matrix and Ca(2+) signaling with or without ATP stimulation in human bone marrow-derived mesenchymal stem cells (hBMSCs). We found that high extracellular Mg(2+) concentration ([Mg(2+)]e) inhibited extracellular matrix mineralization in hBMSCs in vitro. hBMSCs also produced a dose-dependent decrease in the frequency of calcium oscillations during [Mg(2+)]e elevation with a slight suppression on oscillation amplitude. In addition, spontaneous ATP release was inhibited under high [Mg(2+)]e levels and exogenous ATP addition stimulated oscillation reappear. Taken together, our results indicate that high [Mg(2+)]e modulates calcium oscillations via suppression of spontaneous ATP release and inactivates purinergic receptors, resulting in decreased extracellular mineralized matrix deposition in hBMSCs. Therefore, the high magnesium environment created by the rapid corrosion of Mg alloys may result in the dysfunction of calcium-dependent physiology processes and be disadvantageous to hBMSCs physiology.
authors.affiliation: Department of Orthopedics, Tenth People's Hospital, Shanghai Tong Ji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, People's Republic of China; The First Clinical Medical College, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Tenth People's Hospital, Shanghai Tong Ji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, People's Republic of China. Electronic address: chunxi_yang@163.com.
authors.forename: Chunxi
authors.initials: C
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Tenth People's Hospital, Shanghai Tong Ji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, People's Republic of China.
authors.forename: Yuchang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, People's Republic of China. Electronic address: xlzhang@sibs.ac.cn.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008903:Minerals / Q000378:metabolism*
chemical_list: D008903:Minerals; D000255:Adenosine Triphosphate; D008274:Magnesium
keywords: ATP; Bone marrow-derived mesenchymal stem cells; Calcium; Magnesium; Spontaneous calcium oscillations