Abstract

Objective This study is aimed at studying the effect of zoledronate (ZOL) on the differentiation of osteoclast precursor RAW264.7 cells induced by titanium (Ti) particles and explores the possibility of preventing and treating periprosthetic osteoporosis using ZOL. Methods RAW264.7 cells were cultured in vitro. Ti particles were prepared. The cell proliferation curve of RAW264.7 cells was plotted using the MTT assay to find the best concentration of ZOL for intervention. The cells were divided into three groups: control, Ti particles, and Ti particles+ZOL. The cell morphology was observed using tartaric acid–resistant acid phosphatase (TRAP) staining, and the activity of TRAP in cell supernatant was determined using the biochemical method. The number of bone resorption lacunae was detected using toluidine blue staining. The mRNA expression of RANK, NFATcl, CAII, and MMP-9 was detected using real-time polymerase chain reaction. The protein expression of RANK, NFATcl, and MMP-9 was detected using Western blot analysis. Results Ti particles stimulated the differentiation of RAW264.7 cells into osteoclasts. They also increased the activity of TRAP, number of bone resorption lacunae, and mRNA and protein expression of RANK, NFATcl, and MMP-9. However, ZOL could suppress the effect of TI particles on the osteoclast differentiation of RAW264.7 cells. Conclusions ZOL could effectively inhibit the differentiation of RAW264.7 cells into osteoclasts induced by Ti particles, decrease the activity of TRAP, reduce the number of bone resorption lacunae, and decrease the mRNA and protein expression of RANK, NFATcl, and MMP-9. Hence, it may be a promising candidate for preventing and treating periprosthetic osteoporosis after the artificial joint operation.

Highlights

  • The number of hip fractures caused by trauma, osteonecrosis of the femoral head, and osteoporosis has increased with the aging of the population in China

  • Identification of drugs that can inhibit the activation of osteoclasts caused by debris particles to minimize the production of debris particles is important to solve the loosening of the prosthesis caused by periprosthetic osteoporosis

  • ZOL Decreases Osteoclast Differentiation of RAW264.7 Cells Induced by Ti Particles

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Summary

Introduction

The number of hip fractures caused by trauma, osteonecrosis of the femoral head, and osteoporosis has increased with the aging of the population in China. The aseptic loosening of the prosthesis caused by periprosthetic osteoporosis after THA operation is the main factor affecting the stability of the hip joint, the service life of the prosthesis, and the renovation rate [2]. Previous studies demonstrated that the metal and polyethylene liner produced a large number of metal particles and subparticles due to continuous wear after replacement, and the shed particles moved to the bone–prosthesis interface with mechanical fretting. These prosthetic wear particles, such as Ti particles, have been reportedly involved in the initiation and development of periprosthetic osteoporosis by promoting osteoclast differentiation and bone resorption activity [4, 5]. Identification of drugs that can inhibit the activation of osteoclasts caused by debris particles to minimize the production of debris particles is important to solve the loosening of the prosthesis caused by periprosthetic osteoporosis

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