1. Deletion of Opg Leads to Increased Neovascularization and Expression of Inflammatory Cytokines in the Lumbar Intervertebral Disc of Mice.
- Author
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Xiao-Feng Li, Chun-Chun Xue, Yong-Jian Zhao, Shao-Dan Cheng, Dong-Feng Zhao, Qian-Qian Liang, Lin Chen, Qiang Wang, Sheng Lu, Qi Shi, Yong-Jun Wang, Bing Shu, Li, Xiao-Feng, Xue, Chun-Chun, Zhao, Yong-Jian, Cheng, Shao-Dan, Zhao, Dong-Feng, Liang, Qian-Qian, Chen, Lin, and Wang, Qiang
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OSTEOPROTEGERIN , *CELL receptors , *INTERVERTEBRAL disk diseases , *NEOVASCULARIZATION , *CYTOKINES , *ANIMAL experimentation , *INTERVERTEBRAL disk , *LUMBAR vertebrae , *SPINE diseases , *MICE , *PATHOLOGIC neovascularization , *METABOLISM - Abstract
Study Design: Neovascularization and expression of inflammatory cytokines were examined in Osteoprotegerin (Opg) knockout (KO) mice that show intervertebral disc (IVD) degeneration.Objective: The aim of this study was to clarify the pathological changes in lumbar IVD degeneration in Opg KO mice.Summary Of Background Data: Osteoporosis is a controversial risk factor for IVD degeneration. Deletion of Opg resulted in IVD degeneration in mice. Neovascularization and inflammatory cytokines are key factors in IVD degeneration.Methods: Opg KO mice and their wild-type (WT) littermates were euthanized. Lumbar IVDs were harvested. Safranin O/Fast Green staining was performed to examine the pathological changes. Microcomputed tomographic (micro-CT) analysis was performed to determine the structural changes at the junction of lumbar IVD cartilage and vertebrae. Tartrate-resistant acid phosphatase (TRAP) staining was performed to evaluate osteoclast formation. Protein expression of vascular endothelial growth factor A (VEGF-A), CD31, VE-cadherin, CD 34, interleukin-1β (IL-1β), and tumor necrosis factors α (TNF-α) were analyzed by immunohistochemistry (IHC) assays. Gene expressions of IL-1β, IL-6, and TNF-α were analyzed by real-time polymerase chain reaction (RT-PCR).Results: In 12-week-old Opg KO mice, new bone was formed in the endplate cartilage of lumbar IVDs and this became more obvious in 24-week-old Opg KO mice. Three-dimensional (3D) μCT reconstruction analyses showed that the edges of the L4 and L5 vertebrae were rugged with bone marrow cavities in it. Protein expression of VEGF-A, CD31, VE-cadherin, and CD34 was increased in the endplate and growth plate of lumbar IVDs of Opg KO mice. Gene expression of IL-1β, IL-6, and TNF-α as well as protein expression of IL-1β and TNF-α were highly expressed in the lumbar IVDs of Opg KO mice.Conclusion: Deletion of Opg leads to increased neovascularization and expression of inflammatory cytokines in the lumbar disc in Opg KO mice, which may play important roles in IVD degeneration.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]- Published
- 2017
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