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Application of Ferrostatin-1 in preparation of medicine for resisting periprosthetic osteolysis induced by wear particles of joint prosthesis

A technology of joint prosthesis and wear particles, which is applied in the field of biomedicine, can solve problems that have not been reported, and achieve the effects of delaying effectiveness, inhibiting excessive accumulation, and delaying the degree of skull osteolysis

Active Publication Date: 2021-09-28
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, there is no report about the application of Ferrostatin-1 of the present invention in the preparation of anti-articular prosthesis wear particles to induce periprosthetic osteolysis

Method used

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  • Application of Ferrostatin-1 in preparation of medicine for resisting periprosthetic osteolysis induced by wear particles of joint prosthesis
  • Application of Ferrostatin-1 in preparation of medicine for resisting periprosthetic osteolysis induced by wear particles of joint prosthesis
  • Application of Ferrostatin-1 in preparation of medicine for resisting periprosthetic osteolysis induced by wear particles of joint prosthesis

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Embodiment 1

[0039] Example 1 In vivo and in vitro studies of Ferrostatin-1 inhibiting periprosthetic osteolysis induced by wear particles of joint prosthesis

[0040] 1 Materials and methods

[0041] 1.1 Culture of mouse osteoblast cell line

[0042] The mouse osteoblast cell line MC3T3-E1 was purchased from the Institute of Biochemical Cells, Chinese Academy of Sciences. MC3T3-E1 cells are osteoblast precursor cell lines derived from mouse skull, which can differentiate and mature into osteoblasts under the culture of osteogenic induction medium. MC3T3-E1 cells were placed in α-MEM medium (containing 10% fetal bovine serum and 1% penicillin and streptomycin) at 37°C, 5% CO 2 cultured in a cell culture incubator.

[0043] 1.2 Preparation of wear particles for joint prosthesis

[0044] CoCrMo wear particles are ground by Nanjing Kester Metal Products Co., Ltd., with a diameter of 29.30-204.27nm. The CoCrMo particles were sterilized at 180°C for 6 hours, immersed in 75% ethanol for 48 h...

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Abstract

The invention discloses application of Ferrostatin-1 in preparation of a medicine for resisting prosthesis looseness induced by wear particles derived from an artificial joint prosthesis, and research shows that the wear particles of the joint prosthesis can induce excessive accumulation of reactive oxygen species (ROS) in osteoblasts, inhibit the function of an osteoblast cystine / glutamic acid antitransporter (System Xc-), and reduce the ROS removing capability of glutathione peroxidase 4 (GPX4), so that ROS generation and degradation homeostasis are disordered, secondary ferroptosis of osteoblasts is caused, and the balance between osteoclasts and osteoblasts is broken. After the ferroptosis specific inhibitor Ferrostatin-1 is added, the content of the GPX4 in cells is obviously increased, the stimulation of the wear particles to the generation of ROS in the osteoblasts is obviously inhibited, and the ferroptosis of the osteoblasts is reduced. In addition, a mouse skull osteolysis model is established by implanting the CoCrMo nano wear particles under the skin of a mouse skull, effective intervention is applied by intraperitoneal injection of the Ferrostatin-1, and an in-vivo experiment further proves that the Ferrostatin-1 has a remarkable inhibition effect on osteolysis induced by the wear particles.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of Ferrostatin-1 in the preparation of anti-articular prosthesis wear particles to induce periprosthetic osteolysis. Background technique [0002] Artificial joint replacement is one of the important methods for the treatment of advanced osteoarthritis, and has achieved good short-term and long-term effects. However, periprosthetic osteolysis after artificial joint replacement is still a major problem for clinicians. During the long-term use of the artificial joint prosthesis, wear particles (such as titanium, polyethylene, ceramics, etc.) will be produced, and these wear particles will gather on the boundary membrane between the bone and the prosthesis, stimulating various tissues around the prosthesis. Inflammatory reaction leads to enhanced osteoclastosis and weakened bone, leading to an imbalance between bone resorption and osteogenesis, and aseptic loosen...

Claims

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Application Information

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IPC IPC(8): A61K31/245A61K45/00A61P19/08A61P39/06
CPCA61K31/245A61K45/00A61P19/08A61P39/06
Inventor 徐以明马金忠桑伟林朱力波王聪陆海明薛松钟毅鸣毛信杰陈宏杰
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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