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04 March 2016 : Laboratory Research  

Adenovirus-mediated siRNA targeting CXCR2 attenuates titanium particle-induced osteolysis by suppressing osteoclast formation

Chen WangBE, Yang LiuB, Yang WangB, Hao LiF, Ran-Xi ZhangF, Mi-Si HeCD, Liang ChenCD, Ning-Ning WuF, Yong LiaoF, Zhong-Liang DengA

DOI: 10.12659/MSM.897243

Med Sci Monit 2016; 22:727-735

Abstract

BACKGROUND: Wear particle-induced peri-implant loosening is the most common complication affecting long-term outcomes in patients who undergo total joint arthroplasty. Wear particles and by-products from joint replacements may cause chronic local inflammation and foreign body reactions, which can in turn lead to osteolysis. Thus, inhibiting the formation and activity of osteoclasts may improve the functionality and long-term success of total joint arthroplasty. The aim of this study was to interfere with CXC chemokine receptor type 2 (CXCR2) to explore its role in wear particle-induced osteolysis.

MATERIAL AND METHODS: Morphological and biochemical assays were used to assess osteoclastogenesis in vivo and in vitro. CXCR2 was upregulated in osteoclast formation.

RESULTS: Local injection with adenovirus-mediated siRNA targeting CXCR2 inhibited titanium-induced osteolysis in a mouse calvarial model in vivo. Furthermore, siCXCR2 suppressed osteoclast formation both directly by acting on osteoclasts themselves and indirectly by altering RANKL and OPG expression in osteoblasts in vitro.

CONCLUSIONS: CXCR2 plays a critical role in particle-induced osteolysis, and siCXCR2 may be a novel treatment for aseptic loosening.

Keywords: Adenoviridae - metabolism, Bone Marrow Cells - pathology, Macrophages - pathology, Osteoclasts - pathology, Osteogenesis - drug effects, Osteolysis - pathology, Osteoprotegerin - metabolism, RANK Ligand - pharmacology, RAW 264.7 Cells, RNA, Small Interfering - metabolism, Receptors, Interleukin-8B - metabolism, Signal Transduction - drug effects, Skull - pathology, Titanium - adverse effects, Up-Regulation - drug effects

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750