Biological response of $Co^{2+}$ to preosteoblasts during aseptic loosening of the prosthesis

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Jiang, Shengyuan
Li, Dan
Jiang, Jianha
Shang-You, Yang
Yang, Shuye
Jiang, S., Li, D., Jiang, J., Shang-You, Y., & Yang, S. (2021). Biological response of co2+ to preosteoblasts during aseptic loosening of the prosthesis. Chinese Journal of Tissue Engineering Research, 25(21), 3292-3299. doi:10.3969/j.issn.2095-4344.3873
BACKGROUND: Aseptic loosening of prosthesis is the main long-term complication after artificial joint replacement. Metal ions have been proven to be one of the causes of aseptic loosening. How to control and mitigate aseptic loosening is an issue of concern. OBJECTIVE: To observe the biological response of preosteoblasts challenged with $Co^{2+}$ during aseptic loosening of the prosthesis. METHODS: (1) In vitro: Preosteoblasts (MC3T3-E1) of mice were co-cultured with osteoblast induction solution of mice containing different concentrations of $Co^{2+}$ for 72 hours, respectively, and induced into osteoblast cells. The cell proliferation was tested by MTT assay and the cytotoxicity of different concentrations of $Co^{2+}$ was measured with the activity of lactate dehydrogenase. The concentration of alkaline phosphatase protein was used to detect the transformation ability of preosteoblasts. RT-PCR was performed to detect the mRNA expression of related factors. (2) In vivo: Titanium nails were implanted into the proximal tibia of mice. The mice were divided into three groups. Mice in the stable control group were implanted with titanium nails. Mice in the loosening control group were implanted with titanium nails and cobalt-chromium particles. Mice in the cobalt ion group were implanted with titanium nails and cobalt-chromium particles and injected with cobalt-stimulated preosteoblasts. Bone mineral density around prosthesis was detected by MicroCT scanning immediately after surgery. Five weeks later, the bone density around the prosthesis was measured again. The mice were sacrificed and the affected knee joints were dissected for the pull-out test. The tissue after nail pull was stained with hematoxylin and eosin. The looseness of the prosthesis was determined by the force of the nail pull. The degree of inflammation was reflected by the thickness of the membrane between the prosthesis and the bone interface. The number of osteoclasts in the tissues around the prosthesis was observed by anti-tartrate acid phosphatase staining. RESULTS AND CONCLUSION: (1) In vitro results: As the concentration of $Co^{2+}$ increasing, the proliferation of preosteoblasts was decreasing. $Co^{2+}$ had a significant inhibitory effect on serum alkaline phosphatase expression by preosteoblasts. $Co^{2+}$ promoted monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-6, receptor activator of nuclear factor κB ligand, nuclear factor of activated T cells c1 mRNA expression, and inhibited osteoprotegerin and osteoblast specific transcription factor Osterix mRNA expression. Low concentrations of $Co^{2+}$ (62 μmol/L) promoted low density lipoprotein receptor-related protein-5 and Runx2 mRNA expression, but high concentrations of $Co^{2+}$ (500 μmol/L) inhibited their expression. (2) In vivo results: MicroCT scan showed that the mice in cobalt ion group had the lowest bone mineral density (P < 0.05). In the cobalt ion group, the shear force required for pull-out test was significantly lower than that in the control group (P < 0.05). Hematoxylin-eosin staining showed that the formation of periprosthetic inflammatory reaction membrane was significant in the cobalt ion group, stimulation of preosteogenic cells by bivalent cobalt ions may exacerbate the inflammatory response around the prosthesis. (3) These results indicated that osteoblasts can play an important role in the aseptic loosening of the prostheses. $Co^{2+}$ stimulated preosteoblastic cells play an important regulatory role in the differentiation and maturation of osteoclasts.
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