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Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 291 - 291
1 Jul 2014
Ding Y Huang J Huang D Shen H
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Summary. RNAi targeting p110β reduces TNF-alpha production and osteolysis in response to wear particles. Introduction. Aseptic joint loosening is a key factor that reduces the life span of joint prosthesis. Prosthetic wear particles are thought to play a central role in the initiation and development of periprosthetic osteolysis, leading to aseptic loosening of prostheses. This study aims to explore the effect of p110β-targeted small interfering RNA (siRNA) and lentivirus on particle-induced inflammatory cytokine expression in murine macrophage. Methods. siRNA and lentivirus targeting p110β were transfected and infected prior to particle stimulation, respectively. Ceramic and titanium particles of different sizes were prepared to stimulate macrophages. Fluorescence microscopy showed that the siRNA transfection and lentivirus infection efficiency were 74.2 ± 4.2% and 92.3 ± 2.6%, respectively. Results. Real-time polymerase chain reaction (PCR) showed that the levels of tumor necrosis factor-alpha (TNF-alpha) mRNA in the particle stimulation plus RNA interference (RNAi) groups were significantly lower compared with the particle stimulation-only groups (P<0.05), respectively. Similarly, enzyme-linked immunosorbent assay (ELISA) showed that protein levels of TNF-alpha in RNAi-treated groups were significantly decreased after transfection or infection (P<0.05), respectively. Western Blot showed that Phospho-Akt activation was significantly reduced by RNAi. As assessed by CT and micro-CT, particle implantation induced a significant osteolysis effect in mice calvaria, which was limited by p110β-lentivirus addition. Conclusions. p110β subtype of PI3K, followed by activation of phosphor-AKT (Ser473), may possibly participate in the regulation of activating macrophages by wear particles, ultimately resulting in the secretion of TNF-α and osteolysis


Bone & Joint Research
Vol. 7, Issue 6 | Pages 414 - 421
1 Jun 2018
Yu CD Miao WH Zhang YY Zou MJ Yan XF

Objectives

The aim of this study was to investigate the role of miR-126 in the development of osteoarthritis, as well as the potential molecular mechanisms involved, in order to provide a theoretical basis for osteoarthritis treatment and a novel perspective for clinical therapy.

Methods

Human chondrocyte cell line CHON-001 was administrated by different doses of interleukin (IL)-1β to simulate inflammation. Cell viability, migration, apoptosis, IL-6, IL-8, and tumour necrosis factor (TNF)-α expression, as well as expression of apoptosis-related factors, were measured to assess inflammation. miR-126 expression was measured by quantitative polymerase chain reaction (qPCR). Cells were then transfected with miR-126 inhibitor to assess the effect of miR-126 on IL-1β-injured CHON-001 cells. Expression of B-cell lymphoma 2 (Bcl-2) and the activity of mitogen-activated protein kinase (MAPK) / Jun N-terminal kinase (JNK) signaling pathway were measured by Western blot to explore the underlying mechanism through which miR-126 affects IL-1β-induced inflammation.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 173 - 178
1 Feb 2018
Peng X Wu X Zhang J Zhang G Li G Pan X

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis. This review provides a summary of the recent studies on the role of CKIP-1 in osteoporosis development and treatment.

Cite this article: X. Peng, X. Wu, J. Zhang, G. Zhang, G. Li, X. Pan. The role of CKIP-1 in osteoporosis development and treatment. Bone Joint Res 2018;7:173–178. DOI: 10.1302/2046-3758.72.BJR-2017-0172.R1.