Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration

Lin, Sihan; Yin, Shi; Shi, Junfeng; Yang, Guangzheng; Wen, Xutao; Zhang, Wenjie; Zhou, Mingliang; Jiang, Xinquan

doi:10.1016/j.bioactmat.2022.03.024

Cited by 20 publications

(19 citation statements)

References 41 publications

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“…An increase in the intracellular AMP to ATP ratio, as a consequence of decreased intracellular ATP, may be responsible for the activation of AMPK, as well as the subsequent induction of cellular autophagy. Serving as a cofactor of ATP, magnesium plays an important role in regulating glucose metabolism [ 47 ], resulting in a metabolic shift from oxidative phosphorylation to glycolysis [ 48 ]. Compared to oxidative phosphorylation, glycolysis gives rise to faster but lower ATP production [ 49 ], which is consistent with our results showing that there was a significantly decreased amount of ATP with the presence of magnesium.…”

Section: Discussionmentioning

confidence: 99%

AMPK/mTOR Pathway Is Involved in Autophagy Induced by Magnesium-Incorporated TiO2 Surface to Promote BMSC Osteogenic Differentiation

Wang

Luo

Qiao

et al. 2022

JFB

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Magnesium has been extensively utilized to modify titanium implant surfaces based on its important function in promoting osteogenic differentiation. Autophagy has been proven to play a vital role in bone metabolism. Whether there is an association between autophagy and magnesium in promoting osteogenic differentiation remains unclear. In the present study, we focused on investigating the role of magnesium ions in early osteogenic activity and the underlying mechanism related to autophagy. Different concentrations of magnesium were embedded in micro-structured titanium surface layers using the micro-arc oxidation (MAO) technique. The incorporation of magnesium benefited cell adhesion, spreading, and viability; attenuated intracellular ATP concentrations and p-mTOR levels; and upregulated p-AMPK levels. This indicates the vital role of the ATP-related AMPK/mTOR signaling pathway in the autophagy process associated with osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) induced by magnesium modification on titanium surfaces. The enhanced osteogenic differentiation and improved cellular autophagy activity of BMSCs in their extraction medium further confirmed the function of magnesium ions. The results of the present study advance our understanding of the mechanism by which magnesium regulates BMSC osteogenic differentiation through autophagy regulation. Moreover, endowing implants with the ability to activate autophagy may be a promising strategy for enhancing osseointegration in the translational medicine field in the future.

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Section: Discussionmentioning

confidence: 99%

AMPK/mTOR Pathway Is Involved in Autophagy Induced by Magnesium-Incorporated TiO2 Surface to Promote BMSC Osteogenic Differentiation

Wang

Luo

Qiao

et al. 2022

JFB

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“…Released BMP-2 and Mg synergetically acted as energy propellants to increase cellular energetic levels of BMSCs to support osteogenesis via the Akt-glycolysis-Mrs2-mitochondrial axis. 78 Similar to BMP-2, other growth factors like insulin regulate fuel consumption and energy expenditure in metabolically active bone tissues. Insulin regulates osteoblasts' glucose metabolism to control osteocalcin production, promoting bone deposition.…”

Section: Organic Metabolic Drug Release Regulating Cell Metabolismmentioning

confidence: 99%

Cellular metabolism: a link connecting cellular behaviour with the physiochemical properties of biomaterials for bone tissue engineering

et al. 2023

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“…They found that Mg 2+ acts as an “energy propellant” that boosts bioenergetic levels to support osteogenesis, leading to enhanced osteoinductivity of BMP-2. Based on this discovery, they developed microgel composite hydrogels as a low-dose BMP-2/Mg 2+ delivery system ( Lin et al, 2022 ).…”

Section: Biomaterials Involved In the Metabolic Regulation For Bone R...mentioning

confidence: 99%

Metabolic regulation by biomaterials in osteoblast

Kang

Zhang

et al. 2023

Front. Bioeng. Biotechnol.

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The repair of bone defects resulting from high-energy trauma, infection, or pathological fracture remains a challenge in the field of medicine. The development of biomaterials involved in the metabolic regulation provides a promising solution to this problem and has emerged as a prominent research area in regenerative engineering. While recent research on cell metabolism has advanced our knowledge of metabolic regulation in bone regeneration, the extent to which materials affect intracellular metabolic remains unclear. This review provides a detailed discussion of the mechanisms of bone regeneration, an overview of metabolic regulation in bone regeneration in osteoblasts and biomaterials involved in the metabolic regulation for bone regeneration. Furthermore, it introduces how materials, such as promoting favorable physicochemical characteristics (e.g., bioactivity, appropriate porosity, and superior mechanical properties), incorporating external stimuli (e.g., photothermal, electrical, and magnetic stimulation), and delivering metabolic regulators (e.g., metal ions, bioactive molecules like drugs and peptides, and regulatory metabolites such as alpha ketoglutarate), can affect cell metabolism and lead to changes of cell state. Considering the growing interests in cell metabolic regulation, advanced materials have the potential to help a larger population in overcoming bone defects.

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Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration

Cited by 20 publications

References 41 publications

AMPK/mTOR Pathway Is Involved in Autophagy Induced by Magnesium-Incorporated TiO2 Surface to Promote BMSC Osteogenic Differentiation

AMPK/mTOR Pathway Is Involved in Autophagy Induced by Magnesium-Incorporated TiO2 Surface to Promote BMSC Osteogenic Differentiation

Cellular metabolism: a link connecting cellular behaviour with the physiochemical properties of biomaterials for bone tissue engineering

Metabolic regulation by biomaterials in osteoblast

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