Effects of magnesium degradation products on mesenchymal stem cell fate and osteoblastogenesis

Luthringer, Bérengère; Willumeit‐Römer, Regine

doi:10.1016/j.gene.2015.08.028

Cited by 72 publications

(47 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our work highlight that vSMCs would undergo phenotypic adaptation to the leachables of the Mg‐based stents, especially to the liberated magnesium ions. Previously, Mg ions were found to affect the differentiation of the undifferentiated human cells, mesenchymal stem cells and endothelial cells . Under the calcifying condition, the Mg ions were anti‐osteogenic for vSMCs .…”

Section: Discussionmentioning

confidence: 98%

Magnesium ion leachables induce a conversion of contractile vascular smooth muscle cells to an inflammatory phenotype

et al. 2018

View full text Add to dashboard Cite

Phenotype switching is a characteristic response of vascular smooth muscle cells (vSMCs) to the dynamic microenvironment and contributes to all stages of atherosclerotic plaque. Here, we immersed pure magnesium and AZ31 alloy in the completed medium under cell culture condition, applied the resultant leaching extracts to the isolated contractile rat aortic vSMCs and investigated how vSMCs phenotypically responded to the degradation of the magnesium-based stent materials. vSMCs became more proliferative and migratory but underwent more apoptosis when exposed to the degradation products of pure magnesium; while the AZ31 extracts caused less cell division but more apoptosis, thus slowing cell moving and growing. Noticeably, both leaching extracts dramatically downregulated the contractile phenotypic genes at mRNA and protein levels while significantly induced the inflammatory adhesive molecules and cytokines. Exogenously added Mg ions excited similar transformations of vSMCs. With the liberation or supplementation of Mg 2+ , the expression patterns of the pro-contractile transactivator myocardin and the pro-inflammatory transcriptional factor kruppel-like factor 4 (KLF4) were reversed. Overall, the degradation of the Mg-based materials would evoke a shift of the contractile vSMCs to an inflammatory phenotype via releasing Mg ions to induce a transition from the phenotypic control of vSMCs by the myocardin to that by the KLF4.How to cite this article: Zhou Y, Liu X, Huang N, Chen Y. 2019. Magnesium ion leachables induce a conversion of contractile vascular smooth muscle cells to an inflammatory phenotype. J Biomed Mater Res Part B 2019:107B:988-1001.

show abstract

Section: Discussionmentioning

confidence: 98%

Magnesium ion leachables induce a conversion of contractile vascular smooth muscle cells to an inflammatory phenotype

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Mg 2+ has been extensively used for the modification of orthopedics biomaterials due to observations that Mg 2+ can contribute to enhanced osteogenesis 18,41 . Previous studies have speculated that Mg 2+ modulates multiple signaling pathways at different stages in the differentiation process of mesenchymal stem cells toward osteoblast lineage 24,[41][42][43] . For example, Mg 2+ is suggested to promote the proliferation and osteogenic differentiation of MSC by sequentially activating MAPK/ERK signaling pathway and Wnt/β-catenin signaling pathway 43 .…”

Section: Discussionmentioning

confidence: 99%

“…Mg 2+ modified biomaterials have shown superior osteogenic capacity in many reports [14][15][16][17][18][19][20][21] . However, the detrimental effects of Mg 2+ released upon degradation have also been observed [22][23][24] . These conflicting results may reflect the incomplete understanding of the roles of Mg 2+ in the complex biological process of bone healing.…”

Section: Introductionmentioning

confidence: 99%

TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration

Qiao

Wong

Shen

et al. 2020

Preprint

View full text Add to dashboard Cite

The use of magnesium ion (Mg 2+ )-modified biomaterials in bone regeneration is a promising and cost-effective therapeutic. Despite the widespread observation on the osteogenic effects of Mg 2+ , the diverse roles played by Mg 2+ in the complex biological process of bone healing have not been systematically dissected. Here, we reveal a previously unknown biphasic mode of action of Mg 2+ in bone repair. In the early inflammation phase, Mg 2+ primarily targets the monocyte-macrophage lineage to promote their recruitment, activation, and polarization.We showed that an increase in extracellular Mg 2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7) and a TRPM7-dependent influx of Mg 2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines like IL-8, leading to the formation of a pro-osteogenic immune microenvironment. In the later active repair/remodeling phase of bone healing, however, continued exposure of Mg 2+ and IL-8 leads to over activation of NF-κB signaling in macrophages, turning the immune microenvironment into pro-osteoclastogenesis. Moreover, the presence of Mg 2+ at this stage also decelerates bone maturation through the suppression of hydroxyapatite precipitation. The negative effects of Mg 2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg 2+ , as we found prolonged delivery of Mg 2+ compromises overall bone formation. Taken together, this study establishes a paradigm shift in understanding the diverse and multifaceted roles of Mg 2+ in bone healing.

show abstract

“…Magnesium is the second most abundant intracellular divalent cation, 16 being one of the essential elements for living organisms, about 60%-65% of what is found in the human body is present in bones and teeth, and the remaining 35%-40% is spread in the body such as muscle tissue, nerve tissue, and other soft tissue, as well as in physiological fluids.…”

Section: Introductionmentioning

confidence: 99%

“…17 It is involved in various mechanisms through two main methods, being able to interact with the substrate by binding to it and leading to the formation of a substrate/enzyme complex or by binding to enzymes to modify their structure. 16 The study carried out aimed at the preparation and characterization of some ceramic materials on the basis of HAp (Ca 10 (PO 4 ) 6 (OH) 2 ), within which calcium ions are substituted by magnesium ions in order to improve the regenerative properties of the material. The material (HAp-Mg) was obtained by chemical precipitation method using calcium oxide (CaO) and phosphoric acid (H 3 PO 4 ) as precursors.…”

Section: Introductionmentioning

confidence: 99%

Ceramics based on calcium phosphates substituted with magnesium ions for bone regeneration

Ghiţulică

Cucuruz

Voicu

et al. 2019

Int J Applied Ceramic Tech

View full text Add to dashboard Cite

In this study, chemical precipitation methods were used to obtain ceramic materials doped with magnesium ions in order to improve the regeneration properties of materials used for tissue engineering. Two different ratios of magnesium oxide were used to dope the ceramic powder, more precisely 5% and 10%. The synthesized materials were characterized to determine the calcination temperature of the precursor powder by means of thermal analysis; to determine the mineralogical composition, X-ray diffraction was employed and the scanning electron microscopy was used to determine the microstructure. To make use of these ceramics as biomaterials, viability and proliferation cell tests have been performed. Since synthetic materials have several limitations with regard to medical applications, the materials based on HAp substituted with Mg ions are a promising solution for the regeneration of bone defects because they have a similar bone structure. The presence of Mg in the material proves to be beneficial because this element plays an important role in bone cell regeneration, and more specifically, in stimulating osteoblast proliferation. The materials synthesized in this work present a suitable morphology for uses in bone regeneration because they offer to cells a friendly environment for growth and anchoring.

show abstract

Effects of magnesium degradation products on mesenchymal stem cell fate and osteoblastogenesis

Cited by 72 publications

References 45 publications

Magnesium ion leachables induce a conversion of contractile vascular smooth muscle cells to an inflammatory phenotype

Magnesium ion leachables induce a conversion of contractile vascular smooth muscle cells to an inflammatory phenotype

TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration

Ceramics based on calcium phosphates substituted with magnesium ions for bone regeneration

Contact Info

Product

Resources

About