title: Adenovirus-mediated siRNA targeting CXCR2 attenuates titanium particle-induced osteolysis by suppressing osteoclast formation.
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.
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Ran-Xi
authors.initials: RX
authors.lastname: Zhang
authors.affiliation: Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, China (mainland).
authors.forename: Mi-Si
authors.initials: MS
authors.lastname: He
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory Testing Diagnostics, Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Wu
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Yong
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland).
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Deng
mesh_terms: D000256:Adenoviridae / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D005260:Female; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D010014:Osteolysis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D034741:RNA, Small Interfering / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000187:drug effects / Q000473:pathology; D014025:Titanium / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D034741:RNA, Small Interfering; D023063:Receptors, Interleukin-8B; D014025:Titanium