Implant derived high local concentration of magnesium inhibits tumorigenicity of osteosarcoma

Abstract

Osteosarcoma (OS) is a fatal malignant tumor that occurs in bone, whose main treatment is surgical resection. With anti-tumor and osteogenic effects, Magnesium (Mg) is a promising biodegradable metal for postoperative treatment in OS, however, its anti-OS effect and mechanism still need to be explored. Here, while holding the ability to promote osteogenesis, Mg metal at the same time significantly reduces the proliferation, migration and invasion of various OS cells (UMR106, 143B, K7M2) in vitro. Similarly, it inhibits the growth and lung metastasis of UMR106 induced tumors in xenograft models in vivo. The mRNA-seq analysis shows that Mg significantly inhibits Wnt-pathway (increased APC, Axin2 and GSK3β to induce degradation of β-catenin) in typical OS, which is further verified by western blotting and immunofluorescence analyses. A Mg²⁺ concentration of 240 mg/L, either from Mg metal extract or Mg salt (MgCl₂), equivalently exhibits significantly increased APC, Axin2, GSK3β and decreased β-catenin, and then inhibits tumorigenicity of typical OS cells. This work reveals that a local high concentration of Mg can inhibit OS by down-regulating Wnt-pathway, and meanwhile favors for normal health bone, which demonstrates a new approach and mechanism in the treatment of OS with Mg-based biodegradable metals.