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Table 2 The contribution of metal ions to bone and their mode of action

From: Applications of carbon dots and its modified carbon dots in bone defect repair

 

Role

Mechanism of action

References

Li+

Osteogenesis

Lithium has the ability to block the expression of GSK3, a blocker of the Wnt signaling pathway. Other studies showed that lithium acts as an agonist of the Wnt/b-catenin pathway to enhance fracture healing.

[90]

Zn2+

Osteogenesis

It has been discovered that zinc participates in the structural, catalytic, or regulatory aspects of ALP expression, where it is crucial for osteogenesis and mineralization. Additionally, it is thought that zinc has the power to stop the osteoclastic resorption process.

[91,92,93,94]

Mg2+

Osteogenesis, Angiogenesis, Neural stimulation

Magnesium stimulates the synthesis of HIF and PGC-1α in undifferentiated and differentiated hBMSCs, respectively. This promotes the VEGF synthesis.

Mg2+ penetrates DRG neurons, induces the release of CGPR, and subsequently activates PDSCs to produce the osteogenic differentiation-related genes.

[95,96,97,98,99]

Sr2+

Osteogenesis

Strontium stimulates the activity of osteoblastic cells while decreasing the activity of osteoclasts.

It stimulates CaSR and signaling pathways downstream. It enhances the synthesis of OPG and reduces the expression of RANKL. This stimulates osteoblast proliferation, differentiation, and viability and causes osteoclast death, which decreases bone resorption.

[100, 101]

Cu+

Angiogenesis, Osteogenesis

Copper is known to be a factor that induces angiogenesis by imitating hypoxia. Cu2-induced immunological milieu may indirectly promote robust osteogenic differentiation of BMSCs by activating the Oncostation M (OSM) pathway.

[102, 103]

Co2+

Angiogenesis

Co2+ ion is hypothesized to stimulate hypoxia cascade formation, hence stabilizing HIF-1α. The cells will then produce genes (such as VEGF and EPO) that promote neovascularization and angiogenesis in response to this hypoxic environment.

[104,105,106]

Si4+

Angiogenesis, Osteogenesis

Silicon has been demonstrated to stimulate angiogenesis by upregulating NOS, resulting in an increase in VEGF production at low concentrations when human dermal fibroblasts are cultivated.

Osteogenic process is not fully known. However, it has been shown that Si4 at greater concentrations plays a crucial part in the mineralization process.

[107, 108]

  1. Reprinted from Ref. [33]