1.Research progress of magnesium-based biomaterials in the treatment of bone defects induced by osteosarcoma
Jingteng CHEN ; Ling YU ; Shiyu LI ; Weichun GUO
Chinese Journal of Orthopaedics 2025;45(2):109-118
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with a peak incidence between the ages of 10 and 20. It has an extremely high mortality and disability rate. In adults, osteosarcoma is the third most common bone tumor. Despite the advances in chemotherapy, surgical techniques, and radiotherapy that have significantly improved the overall survival rate of osteosarcoma, the long-term prognosis of patients has not shown substantial improvement, especially in cases of tumor metastasis and recurrence. Due to the highly invasive growth of tumor cells, the progression of osteosarcoma is often accompanied by the destruction of surrounding bone tissue and the formation of immature new bone, making treatment challenging, especially in tissue repair and functional recovery following surgical resection. Tumor resection surgery often results in extensive bone loss, particularly in cases involving joints or weight-bearing areas, making the reconstruction of bone structure and function highly complex. Currently, inert materials such as stainless steel or titanium alloy prostheses used in clinical practice exhibit poor biocompatibility and high elastic modulus, often leading to prosthesis loosening and infection. There is an urgent clinical need for multifunctional biomaterials capable of both repairing bone defects and inhibiting tumor recurrence. Magnesium-based biomaterials have shown excellent biodegradability and bioactivity, and the release of magnesium ions and degradation products effectively promotes bone tissue regeneration while demonstrating potential antitumor effects. This paper reviews the application of magnesium-based biomaterials in the treatment of bone defects associated with osteosarcoma, including their adaptation to the acidic conditions of the osteosarcoma microenvironment, their potential to promote osteogenesis, and their antitumor mechanisms. It also analyzes the mechanical compatibility of magnesium-based materials and the use of coating technologies to enhance their corrosion resistance, and explores the prospects of various types of magnesium-based compounds in the treatment of osteosarcoma-related bone defects.
2.Research progress of magnesium-based biomaterials in the treatment of bone defects induced by osteosarcoma
Jingteng CHEN ; Ling YU ; Shiyu LI ; Weichun GUO
Chinese Journal of Orthopaedics 2025;45(2):109-118
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with a peak incidence between the ages of 10 and 20. It has an extremely high mortality and disability rate. In adults, osteosarcoma is the third most common bone tumor. Despite the advances in chemotherapy, surgical techniques, and radiotherapy that have significantly improved the overall survival rate of osteosarcoma, the long-term prognosis of patients has not shown substantial improvement, especially in cases of tumor metastasis and recurrence. Due to the highly invasive growth of tumor cells, the progression of osteosarcoma is often accompanied by the destruction of surrounding bone tissue and the formation of immature new bone, making treatment challenging, especially in tissue repair and functional recovery following surgical resection. Tumor resection surgery often results in extensive bone loss, particularly in cases involving joints or weight-bearing areas, making the reconstruction of bone structure and function highly complex. Currently, inert materials such as stainless steel or titanium alloy prostheses used in clinical practice exhibit poor biocompatibility and high elastic modulus, often leading to prosthesis loosening and infection. There is an urgent clinical need for multifunctional biomaterials capable of both repairing bone defects and inhibiting tumor recurrence. Magnesium-based biomaterials have shown excellent biodegradability and bioactivity, and the release of magnesium ions and degradation products effectively promotes bone tissue regeneration while demonstrating potential antitumor effects. This paper reviews the application of magnesium-based biomaterials in the treatment of bone defects associated with osteosarcoma, including their adaptation to the acidic conditions of the osteosarcoma microenvironment, their potential to promote osteogenesis, and their antitumor mechanisms. It also analyzes the mechanical compatibility of magnesium-based materials and the use of coating technologies to enhance their corrosion resistance, and explores the prospects of various types of magnesium-based compounds in the treatment of osteosarcoma-related bone defects.
3.Notch signaling pathway regulates osteosarcoma stem cell characteristics by inhibiting Eph pathway
Tian GAO ; Zhiwei FANG ; Ling YU ; Jingteng CHEN ; Jiayong LIU ; Shu LI ; Chujie BAI ; Ruifeng XUE ; Lu ZHANG ; Weichun GUO ; Zhengfu FAN
Chinese Journal of Orthopaedics 2018;38(10):612-619
Objective To investigate the role of Notch signaling pathway to maintain the stem cell-like characteristics of osteosarcoma and its underlying mechanism.Methods Lentiviral NICD1 or Numb-shRNA was transduced into MG63 osteosarcoma cells to activate Notch activity in vitro.The impact of Notch on osteosarcoma stem cells were assessed by the tumor sphere formation assay and flow cytometry analysis of cell surface markers STRO-1/CD117.The expression of stem cell related genes (Sox2,Oct4) were evaluated by Western blot and qPCR.The nude mice were randomly divided into 3 groups:the NICD1 overexpression (NICD-OE) group,the DAPT group and the control (CON) group.The tumor growth was monitored for 8 weeks and the tumor volume and weight were recorded weekly.To investigate whether Notch regulates Eph pathway,Eph pathway related protein EphB,pEphB was measured by Western blot.The impact of ephrinB 1 on NICD overexpression cell were assessed by tumor sphere formation assay.The expression of Sox2 and Oct4 was evaluated by Western blot.Results NICD1 overexpression or Numb-shRNA increased the activity of Notch pathway.The Notch-activated osteosarcoma showed enhanced in vitro tumor spheroid formation capacity,increased Stro-1/CD117double positive ratio,and upregulated expression of Sox2 and Oct4 in vitro.In animal experiments,it was found that activation of Notch pathway promoted tumor formation in vivo and Notch inhibition decreased it.The primary osteosarcoma cells were obtained from mice xenograft treated with DAPT and its tumor sphere formation capacity was significantly reduced.Finally,The Notch pathway inhibits the phosphorylation of EphB,as well as the downstream signal pathway of EphB,but there is no significant change in total EphB.The activation of Eph pathway inhibited Notch induced up-regulation of tumor sphere formation and Sox2 and Oct4 expression.Conclusion Notch signaling pathway maintains the stem cell-like characteristics of osteosarcoma probably by inhibiting the Eph pathway.

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