Magnesium Chloride promotes Osteogenesis through Notch signaling activation and expansion of Mesenchymal Stem Cells

Díaz-Tocados, Juan Miguel; Herencia, Carmen; Martínez-Moreno, Julio M.; de, Addy Montes; Rodríguez‐Ortiz, María E.; Vergara, Noemí; Blanco, Alfonso; Steppan, Sonja; Almadén, Yolanda; Rodríguez, Mariano; Muñoz‐Castañeda, Juan R.

doi:10.1038/s41598-017-08379-y

Cited by 107 publications

(82 citation statements)

References 29 publications

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“…Cell Culture and Alizarin Red S Staining : BMMSCs were harvested from the femurs of 6 week old B6/C57 mice using the method described previously after euthanasia by sodium pentobarbital. Briefly, after the femurs were carefully washed, the bone marrow was flushed using alpha Dulbecco's modified Eagle's medium (α‐MEM, HyClone).…”

Section: Methodsmentioning

confidence: 99%

Dual Function of Magnesium in Bone Biomineralization

Zhang

Tang

et al. 2019

Adv Healthcare Materials

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infections, and biochemical disorders could be addressed with a wide variety of bone substitutes or implants. [1] Bone is a mineralized composite of inorganic and organic units, mostly hydroxyapatite (HA) and type I collagen, respectively. [2] To mimic the nature of bone, scientists have researched several aspects of the biomaterials of bone substitutes or implants over the past decades, [3] and chemical composition of them is a primary consideration. Currently, magnesium (Mg 2+ ) and Mg 2+ alloys are gaining increasing research interest due to their promising merits, such as biodegradability, relatively slow corrosion rates, and suitable mechanical properties. [4] However, the osteoinductive effect of Mg 2+ alloys could not be directly determined due to complex alloy constituents, complicated surface modification technology, and intricate physiological microenvironments.A bone mineral precursor, amorphous calcium phosphate (ACP), could be fabricated with Mg 2+ ions, which act as an ACP phase stabilizer to maintain a noncrystal phase. [5] Mg 2+ could partially substitute Ca 2+ ions in the apatite structure and inhibit ACP transformation into HA. [5a] Chemically, it has been shown that Mg 2+ ions retard the crystallization of ACP and control the final aging of crystals. [5c] Moreover, Mg 2+ is considered the main intracellular antagonist of Ca 2+ . [6] Hence, there is an unreasonable paradox that Mg 2+ exerts its role during bone formation as an indispensable element due to its inhibitory effects on biomineralization, which were ignored by previous studies. [6,7] Thus, logically, Mg 2+ is proposed to have a complicated connection with osteogenesis.To answer this question derived from the field of regenerative and bioengineering medicine, the best approach is to investigate development, which could subsequently guide regeneration. [2,8] Mineralization development is a kind of complex chemical reaction among calcium (Ca 2+ ), phosphate (PO 4 3− ), Mg 2+ , and some amino acids. [2] Among the bones in vertebrates, the cranial bone is unique because it provides spaces, support, and protection for soft brain tissues, and has two different developmental mechanisms, namely, endochondral and intramembranous ossification. [9] Therefore, the development of the skull is a proper model. [10] Numerous studies have demonstrated that several kinds of factors play explicit roles during cranial development, [8,9,11] but which elements and how these elements influence the formation and mineralization of the skull, in particular, HA and type I collagen, are not well defined.Magnesium (Mg 2+ ), as a main component of bone, is widely applied to promote bone growth and regeneration. However, Mg 2+ can chemically inhibit the crystallization of amorphous calcium phosphate into hydroxyapatite (HA). The underlying mechanisms by which Mg 2+ improves bone biomineralization remain elusive. Here, it is demonstrated that Mg 2+ plays dual roles in bone biomineralization from a developmental perspective. During embryonic development, the Mg 2+ ...

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Section: Methodsmentioning

confidence: 99%

Dual Function of Magnesium in Bone Biomineralization

Zhang

Tang

et al. 2019

Adv Healthcare Materials

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“…Alterations in Mg 2+ homeostasis are implicated in changes in the differentiation process of MSCs; whereas their increase promotes osteoblastogenesis, Mg 2+ deficiency appears to be detrimental to bone health [ 74 , 75 ]. In BMSCs from experimental models, an increase in Mg 2+ concentration elevated the expression of RUNX2, OSTERIX , and OSTEOCALCIN genes, increased the levels of cyclin D1 and proliferating cell nuclear antigen (PCNA) proteins, and induced the activation of Notch signaling [ 31 ]. Studies with osteoblasts from animal models verified that 6 mM and 10 mM Mg 2+ upregulated RUNX2, BMP2, ALP, OPN , and COL1 expression and increased the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway [ 32 ].…”

Section: The Role Of Mg 2+ In Hematopoiesismentioning

confidence: 99%

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

Lima

Fock

2020

IJMS

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Magnesium (Mg2+) is an essential mineral for the functioning and maintenance of the body. Disturbances in Mg2+ intracellular homeostasis result in cell-membrane modification, an increase in oxidative stress, alteration in the proliferation mechanism, differentiation, and apoptosis. Mg2+ deficiency often results in inflammation, with activation of inflammatory pathways and increased production of proinflammatory cytokines by immune cells. Immune cells and others that make up the blood system are from hematopoietic tissue in the bone marrow. The hematopoietic tissue is a tissue with high indices of renovation, and Mg2+ has a pivotal role in the cell replication process, as well as DNA and RNA synthesis. However, the impact of the intra- and extracellular disturbance of Mg2+ homeostasis on the hematopoietic tissue is little explored. This review deals specifically with the physiological requirements of Mg2+ on hematopoiesis, showing various studies related to the physiological requirements and the effects of deficiency or excess of this mineral on the hematopoiesis regulation, as well as on the specific process of erythropoiesis, granulopoiesis, lymphopoiesis, and thrombopoiesis. The literature selected includes studies in vitro, in animal models, and in humans, giving details about the impact that alterations of Mg2+ homeostasis can have on hematopoietic cells and hematopoietic tissue.

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“…While the link between Mg and cell growth has been deeply investigated, comparatively little is known on the role of this element in cell differentiation. A few studies suggest that extracellular Mg differently affects cell differentiation [ 7 , 8 , 9 , 10 ]. Recently, intriguing results were obtained in human embryonic stem cells [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Magnesium Deprivation Potentiates Human Mesenchymal Stem Cell Transcriptional Remodeling

Sargenti

Castiglioni

Olivi

et al. 2018

IJMS

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Magnesium plays a pivotal role in energy metabolism and in the control of cell growth. While magnesium deprivation clearly shapes the behavior of normal and neoplastic cells, little is known on the role of this element in cell differentiation. Here we show that magnesium deficiency increases the transcription of multipotency markers and tissue-specific transcription factors in human adipose-derived mesenchymal stem cells exposed to a mixture of natural molecules, i.e., hyaluronic, butyric and retinoid acids, which tunes differentiation. We also demonstrate that magnesium deficiency accelerates the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. We argue that magnesium deprivation generates a stressful condition that modulates stem cell plasticity and differentiation potential. These studies indicate that it is possible to remodel transcription in mesenchymal stem cells by lowering extracellular magnesium without the need for genetic manipulation, thus offering new hints for regenerative medicine applications.

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Magnesium Chloride promotes Osteogenesis through Notch signaling activation and expansion of Mesenchymal Stem Cells

Cited by 107 publications

References 29 publications

Dual Function of Magnesium in Bone Biomineralization

Dual Function of Magnesium in Bone Biomineralization

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

Magnesium Deprivation Potentiates Human Mesenchymal Stem Cell Transcriptional Remodeling

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