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

Acta Biomaterialia
Mei LiChuanbin Mao

Abstract

Giant Cell Tumors of Bone (GCTB) are benign but aggressive and metastatic tumors. Surgical removal cannot eradicate GCTB due to the subsequent recurrence and osteolysis. Here we developed Zoledronic acid (ZA)-loaded magnesium-strontium (Mg-Sr) alloys that can inhibit GCTB and studied the molecular and cellular mechanisms of such inhibition. We first formed a calcium phosphate (CaP) coating on the Mg-1.5 wt%Sr implants by coprecipitation and then loaded ZA on the CaP coating. We examined the response of GCTB cells to the ZA-loaded alloys. At the cellular level, the alloys not only induced apoptosis and oxidative stress of GCTB cells, and suppressed their resultant pre-osteoclast recruitment, but also inhibited their migration. At the molecular level, the alloys could significantly activate the mitochondrial pathway and inhibit the NF-κB pathway in the GCTB cells. These collectively enable the ZA-loaded alloys to suppress GCTB cell growth and osteolysis, and thus improve our understanding of the materials-induced tumor inhibition. Our study shows that ZA-loaded alloys could be a potential implant in repairing the bone defects after tumor removal in GCTB therapy. In clinics, giant cell tumors of bone (GCTB) are removed by surgery....Continue Reading

Citations

Apr 9, 2019·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Natalia AnisimovaYuri Estrin
Nov 7, 2019·Advanced Healthcare Materials·Yutao CuiJianxun Ding
Aug 28, 2021·Frontiers in Cell and Developmental Biology·Xudong WangZiji Zhang

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