title: Magnesium Ions Promote the Biological Behaviour of Rat Calvarial Osteoblasts by Activating the PI3K/Akt Signalling Pathway.
abstract: Magnesium has been investigated as a biodegradable metallic material. Increased concentrations of Mg2+around magnesium implants due to biodegradation contribute to its satisfactory osteogenic capacity. However, the mechanisms underlying this process remain elusive. We propose that activation of the PI3K/Akt signalling pathway plays a role in the Mg2+-enhanced biological behaviours of osteoblasts. To test this hypothesis, 6, 10 and 18 mM Mg2+was used to evaluate the stimulatory effect of Mg2+on osteogenesis, which was assessed by evaluating cell adhesion, cell viability, ALP activity, extracellular matrix mineralisation and RT-PCR. The expression of p-Akt was also determined by western blotting. The results showed that 6 and 10 mM Mg2+elicited the highest stimulatory effect on cell adhesion, cell viability and osteogenic differentiation as evidenced by cytoskeletal staining, MTT assay results, ALP activity, extracellular matrix mineralisation and expression of osteogenic differentiation-related genes. In contrast, 18 mM Mg2+had an inhibitory effect on the behaviour of osteoblasts. Furthermore, 10 mM Mg2+significantly increased the phosphorylation of Akt in osteoblasts. Notably, the aforementioned beneficial effects produced by 10 mM Mg2+were abolished by blocking the PI3K/Akt signalling pathway through the addition of wortmannin. In conclusion, these results demonstrate that 6 mM and 10 mM Mg2+can enhance the behaviour of osteoblasts, which is at least partially attributed to activation of the PI3K/Akt signalling pathway. Furthermore, a high concentration (18 mM Mg2+) showed an inhibitory effect on the biological behaviour of osteoblasts. These findings advance the understanding of cellular responses to biodegradable metallic materials and may attract greater clinical interest in magnesium.
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, 463 Hospital of PLA, Shenyang, 110042, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Feng
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
authors.forename: Zhen-Sheng
authors.initials: ZS
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
authors.forename: Tian-Cheng
authors.initials: TC
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Mechanical Engineering, State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. wanglinxj@fmmu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. leiwei@fmmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000469:Alkaline Phosphatase; D008274:Magnesium
keywords: Akermanite; DMEM Culture Medium; Osteogenic Capacity; Osteogenic Differentiation; Wortmannin