Magnesium modification of a calcium phosphate cement alters bone marrow stromal cell behavior via an integrin-mediated mechanism

Zhang, Jing; Ma, Xiaoyu; Lin, Dan; Shi, Hengsong; Yuan, Yuan; Tang, Wei; Zhou, Hao; Guo, Han; Qian, Jiangchao; Liu, Changsheng

doi:10.1016/j.biomaterials.2015.02.097

Cited by 186 publications

(121 citation statements)

References 49 publications

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“…Among the multiple integrins, α5β1 could selectively bind to fibronectin to engage the cells and successively activate the focal adhesion kinase (FAK)48. Available evidence indicated that FAK plays a crucial role in integrating integrin signals to direct ERK signaling activation, RUNX2 transcription, and then osteogenic differentiation of osteoblasts49. Ca 2+ and Sr 2+ could promote osteogenesis via binding to calcium-sensing receptor (CaSR).…”

Section: Discussionmentioning

confidence: 99%

Stimulatory effects of the degradation products from Mg-Ca-Sr alloy on the osteogenesis through regulating ERK signaling pathway

et al. 2016

Sci Rep

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The influence of Mg-1Ca-xwt.% Sr (x = 0.2, 0.5, 1.0, 2.0) alloys on the osteogenic differentiation and mineralization of pre-osteoblast MC3T3-E1 were studied through typical differentiation markers, such as intracellular alkaline phosphatase (ALP) activity, extracellular collagen secretion and calcium nodule formation. It was shown that Mg-1Ca alloys with different content of Sr promoted cell viability and enhanced the differentiation and mineralization levels of osteoblasts, and Mg-1Ca-2.0Sr alloy had the most remarkable and significant effect among all. To further investigate the underlying mechanisms, RT-PCR and Western Blotting assays were taken to analyze the mRNA expression level of osteogenesis-related genes and intracellular signaling pathways involved in osteogenesis, respectively. RT-PCR results showed that Mg-1Ca-2.0Sr alloy significantly up-regulated the expressions of the transcription factors of Runt-related transcription factor 2 (RUNX2) and Osterix (OSX), Integrin subunits, as well as alkaline phosphatase (ALP), Bone sialoprotein (BSP), Collagen I (COL I), Osteocalcin (OCN) and Osteopontin (OPN). Western Blotting results suggested that Mg-1Ca-2.0Sr alloy rapidly induced extracellular signal-regulated kinase (ERK) activation but showed no obvious effects on c-Jun N terminal kinase (JNK) and p38 kinase of MAPK. Taken together, our results demonstrated that Mg-1Ca-2.0Sr alloy had excellent biocompatibility and osteogenesis via the ERK pathway and is expected to be promising as orthopedic implants and bone repair materials.

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Section: Discussionmentioning

confidence: 99%

Stimulatory effects of the degradation products from Mg-Ca-Sr alloy on the osteogenesis through regulating ERK signaling pathway

et al. 2016

Sci Rep

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“…Cytotoxicity was carried out by LDH assay after incubation for 24 h using a cytotoxicity detection kit (Sigma) [53]. DNA contents were measured with the Cyquant cell proliferation assay kit (C7026, Invitrogen) after incubation for 24 h [54]. Cell viability was conducted by Live/Dead Viability g kit (ThermoFisher Scientific) after incubation for 24 h as we described previously [15].…”

Section: Methodsmentioning

confidence: 99%

Molecular and cellular mechanisms for zoledronic acid-loaded magnesium-strontium alloys to inhibit giant cell tumors of bone

Wang

Zhu

et al. 2018

Acta Biomaterialia

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In clinics, giant cell tumors of bone (GCTB) are removed by surgery. However, the resultant defects in bone still contain aggressive and metastatic GCTB cells that can recruit osteoclasts to damage bone, leading to new GCTB tumor growth and bone damage after tumor surgery. Hence, it is of high demand in developing a material that can not only fill the bone defects as an implant but also inhibit GCTB in the defect area as a therapeutic agent. More importantly, the molecular and cellular mechanism by which such a material inhibits GCTB growth has never been explored. To solve these two problems, we prepared a new biomaterial, the Mg-Sr alloys that were first coated with calcium phosphate and then loaded with a tumor-inhibiting molecule (Zoledronic acid, ZA). Then, by using a variety of molecular and cellular biological assays, we studied how the ZA-loaded alloys induced the death of GCTB cells (derived from patients) and inhibited their growth at the molecular and cellular level. At the cellular level, our results showed that ZA-loaded Mg-Sr alloys not only induced apoptosis and oxidative stress of GCTB cells, and suppressed their induced pre-osteoclast recruitment, but also inhibited their migration. At the molecular level, our data showed that ZA released from the ZA-loaded Mg-Sr alloys could significantly activate the mitochondrial pathway and inhibit the NF-κB pathway in the GCTB cells. Both mechanisms collectively induced GCTB cell death and inhibited GCTB cell growth. This work showed how a biomaterial inhibit tumor growth at the molecular and cellular level, increasing our understanding in the fundamental principle of materials-induced cancer therapy. This work will be interesting to readers in the fields of metallic materials, inorganic materials, biomaterials and cancer therapy.

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“…into amorphous silica walls exhibited stimulation effects on osteoblast differentiation and therefore the formation of new bone in vivo. 13,14 Furthermore, the incorporation of Mg-containing particles into scaffolds could tailor a number of important properties, such as crystallinity and degradation, to satisfy the requirements for bone tissue engineering. 15 It is therefore expected that incorporation of m-MS into PBSu scaffolds could modify its properties and overcome the above limitations of using PBSu scaffolds alone for bone regeneration.…”

Section: Introductionmentioning

confidence: 99%

Effects of magnesium silicate on the mechanical properties, biocompatibility, bioactivity, degradability, and osteogenesis of poly(butylene succinate)-based composite scaffolds for bone repair

Zheng

Zhang

et al. 2016

J. Mater. Chem. B

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Bioactive scaffolds of magnesium silicate (m-MS)/poly(butylene succinate) (PBSu) composites were fabricated by a solvent casting-particulate leaching method for bone regeneration. The scaffolds had a hierarchical porous structure with interconnected macropores (300-500 mm), micropores (1-10 mm) and mesopores (B5 nm). In addition, the composite scaffolds were degradable in Tris-HCl solution and The results demonstrated that the bioactive m-MS/PBSu composite scaffolds with good biocompatibility, degradability, bioactivity and osteogenesis are promising biomaterials for bone repair.

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Magnesium modification of a calcium phosphate cement alters bone marrow stromal cell behavior via an integrin-mediated mechanism

Cited by 186 publications

References 49 publications

Stimulatory effects of the degradation products from Mg-Ca-Sr alloy on the osteogenesis through regulating ERK signaling pathway

Stimulatory effects of the degradation products from Mg-Ca-Sr alloy on the osteogenesis through regulating ERK signaling pathway

Molecular and cellular mechanisms for zoledronic acid-loaded magnesium-strontium alloys to inhibit giant cell tumors of bone

Effects of magnesium silicate on the mechanical properties, biocompatibility, bioactivity, degradability, and osteogenesis of poly(butylene succinate)-based composite scaffolds for bone repair

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