• 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, and Bing Shu.
• *Longhua Hospital, Shanghai University of T.C.M., Shanghai, China, 200032 †Spine Research Institute, Shanghai University of T.C.M., Shanghai, China, 200032.
• Spine. 2016 May 18.

Study DesignNeovascularization and expression of inflammatory cytokines were examined in Osteoprotegerin (Opg) knockout (KO) mice which show intervertebral disc (IVD) degeneration.ObjectiveTo clarify the pathological changes in lumbar IVD degeneration in Opg KO mice.Summary Of Background DataOsteoporosis 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.MethodsOpg 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. 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 expression of interleukin-1β (IL-1β), IL-6 and tumor necrosis factors α (TNF-α) were analyzed by real-time polymerase chain reaction (RT-PCR).ResultsIn 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 were 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.ConclusionDeletion 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 EvidenceN/A.

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