Ion channel functional protein kinase TRPM7 regulates Mg ions to promote the osteoinduction of human osteoblast via PI3K pathway: In vitro simulation of the bone-repairing effect of Mg-based alloy implant

Zhang, Xiuzhi; Zu, Haiyue; Zhao, Dewei; Yang, Ke; Tian, Simiao; Yu, Xiaoming; Lu, Fangfang; Liu, Baoyi; Yu, Xiaobing; Wang, Benjie; Wang, Wei; Huang, Shibo; Wang, Yongxuan; Wang, Zihua; Zhang, Zhaodong

doi:10.1016/j.actbio.2017.08.051

Cited by 119 publications

(72 citation statements)

References 47 publications

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“…In addition to providing transmembraneous Ca 2+ flux, TRPM7 is supposed to be upregulating phosphoinositol3-kinse (PI3K; shown to be involved in fibroblast motility; Allen et al, 2013) and protein kinase B (PKB/AKT) pathways, and consecutively growth factor transcription (Zhang et al, 2017). Importantly, upregulation of TRPM7 (in the cited study by using platelet derived growth factor, PDGF) can increase osteoblast motility ).…”

Section: Discussionmentioning

confidence: 98%

Human Osteoblast Migration in DC Electrical Fields Depends on Store Operated Ca2+-Release and Is Correlated to Upregulation of Stretch-Activated TRPM7 Channels

Rohde

Ziebart

Kirschstein

et al. 2019

Front. Bioeng. Biotechnol.

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Fracture healing and bone regeneration, particularly in the elderly, remains a challenge. There is an ongoing search for methods to activate osteoblasts, and the application of electrical fields is an attractive approach in this context. Although it is known that such electromagnetic fields lead to osteoblast migration and foster mesenchymal osteogenic differentiation, so far the mechanisms of osteoblast activation remain unclear. Possible mechanisms could rely on changes in Ca 2+ -influx via ion channels, as these are known to modulate osteoblast activity, e.g., via voltage-sensitive, stretch-sensitive, transient-receptor-potential (TRP) channels, or store-operated release. In the present in vitro study, we explored whether electrical fields are able to modulate the expression of voltage-sensitive calcium channels as well as TRP channels in primary human osteoblast cell lines. We show migration speed is significantly increased in stimulated osteoblasts (6.4 ± 2.1 µm/h stimulated, 3.6 ± 1.1 µm/h control), and directed toward the anode. However, within a range of 154-445 V/m, field strength did not correlate with migration velocity. Neither was there a correlation between electric field and voltage-gated calcium channel (Ca v 3.2 and Ca v 1.4) expression. However, the expression of TRPM7 significantly correlated positively to electric field strength. TRPM7 channel blockade using NS8593, in turn, did not significantly alter migration speed, nor did blockade of Ca v 3.2 and Ca v 1.4 channels using Ni + or verapamil, respectively, while a general Ca 2+ -influx block using Mg 2+ accelerated migration. Stimulating store-operated Ca 2+ -release significantly reduced migration speed, while blocking IP3 had only a minor effect (at low and high concentrations of 2-APB, respectively). We conclude that (i) store operated channels negatively modulate migration speed and that (ii) the upregulation of TRPM7 might constitute a compensatory mechanism-which might explain how increasing expression levels at increasing field strengths result in constant migration speeds.

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Section: Discussionmentioning

confidence: 98%

Human Osteoblast Migration in DC Electrical Fields Depends on Store Operated Ca2+-Release and Is Correlated to Upregulation of Stretch-Activated TRPM7 Channels

Rohde

Ziebart

Kirschstein

et al. 2019

Front. Bioeng. Biotechnol.

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“…apart from those four genes, runx2, another downstream gene of p38 pathway, is also considered as a key effector and marker of osteoblast differentiation (3,4). its transcription also reported to be influenced by other pathways like TRPM7/PI3K signaling pathway (38,39). Transient receptor potential M-type 7 (TrPM7), a non-selective cationic channel with constitutive activity, is an important regulator of entry of several extracellular metal ions, and serves an important regulatory role in bone sclerosis and remodeling (38).…”

Section: Discussionmentioning

confidence: 99%

MgCl2 promotes mouse mesenchymal stem cell osteogenic differentiation by activating the p38/Osx/Runx2 signaling pathway

Xiong

2020

Mol Med Rep

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Magnesium, an important inorganic mineral component in bones, enhances osteoblast adhesion and osteogenic gene expression. Mg 2+-containing hydroxyapatite promotes mouse mesenchymal stem cell (MMSc) osteogenic differentiation. in the present study, MMScs were cultured in media containing different concentrations of Mgcl 2 (0 and 20 mM) for different time periods. Western blotting and reverse transcription-quantitative Pcr were performed to determine the expression levels of phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK), the osteoblast-specific transcription factor osterix (osx), runt-related transcription factor 2 (runx2), and p38 downstream genes, such as 27 kda heat shock protein (hsp27), activating transcription factor 4 (atf4), myocyte enhancer factor 2c (Mef2c) and ccaaT/enhancer-binding protein homologous protein (ddit3). The facilitatory effect of Mgcl 2 on MMSc osteogenic differentiation was assessed via alizarin red staining. The results suggested that Mgcl 2 increased p38 phosphorylation compared with the control group. downstream genes of the p38 signaling pathway, including osx and runx2, as well as several osteogenesis-associated downstream target genes, including Hsp27, atf4, ddit3 and Mef2c, were significantly upregulated in the Mg 2+-treated group compared with the control group. The increased osteogenic differentiation in the Mg 2+-treated group was significantly attenuated in MMSCs treated with SB203580, a specific inhibitor of the p38 signaling pathway. The results suggested that appropriate concentrations of Mgcl 2 promoted MMSc osteogenic differentiation via regulation of the p38/osx/runx2 signaling pathway.

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“…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 ]. In addition to RUNX2 and ALP , researchers showed in hFOB1.19 human osteoblast cells that increased of Mg 2+ ions might also enhance osteoblastogenesis across the TRPM7/PI3K signaling pathway, as PI3K phosphorylation occurs via TRPM7 and leads to the migration of osteoblasts, whereas knockdown of TRPM7 gene decreased alkaline phosphatase (ALP) activity [ 33 ].…”

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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Ion channel functional protein kinase TRPM7 regulates Mg ions to promote the osteoinduction of human osteoblast via PI3K pathway: In vitro simulation of the bone-repairing effect of Mg-based alloy implant

Cited by 119 publications

References 47 publications

Human Osteoblast Migration in DC Electrical Fields Depends on Store Operated Ca2+-Release and Is Correlated to Upregulation of Stretch-Activated TRPM7 Channels

Human Osteoblast Migration in DC Electrical Fields Depends on Store Operated Ca2+-Release and Is Correlated to Upregulation of Stretch-Activated TRPM7 Channels

MgCl2 promotes mouse mesenchymal stem cell osteogenic differentiation by activating the p38/Osx/Runx2 signaling pathway

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

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