Deletion of Opg Leads to Increased Neovascularization and Expression of Inflammatory Cytokines in the Lumbar Intervertebral Disc of Mice

Li, Xiaofeng; Xue, Cong; Zhao, Yongjian; Cheng, Shao-Dan; Zhao, Dongfeng; Liang, Qianqian; Chen, Lin; Wang, Qiang; Lü, Sheng; Shi, Qi; Wang, Yongjun; Shu, Bing

doi:10.1097/brs.0000000000001701

Cited by 16 publications

(13 citation statements)

References 55 publications

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“…Many risk factors have been found to be involved in the IVDD process, including age, sex, injury, obesity, genetic predisposition, immune, nutrition, inflammation, and mechanical factors [ 7 , 24 , 39 ]. Increasing evidence indicates that IVDD is associated with the disruption of an intact spinal structure, such as adjacent structures including the vertebra and endplate [ 14 , 16 , 17 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Rodriguez et al [ 36 ] found that porosity and permeability of the endplate were increased with age and disc degeneration. Osteoprotegerin (OPG) knockdown mice had an increase in neovascularization and expression of inflammatory cytokines in the intervertebral disc, indicating that osteoporosis can induce inflammation and consequently become the cause of disc degeneration [ 24 ]. The modic change of the endplate is closely related to back pain [ 1 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…The osteoporosis of vertebrae in postmenopausal women was correlated with IVDD [ 20 , 21 ], and sex hormones can affect the severity of IVDD [ 21 – 23 ]. Furthermore, in osteoprotegerin (OPG) knockout mice, ossification occurred in the cartilage endplate and resulted in IVDD [ 24 ]. IVDD often occurs with osteoporosis of the vertebrae, indicating that the development of osteoporosis and IVDD might be a coupling process which could explain why postmenopausal women have more lower back pain than men.…”

Section: Introductionmentioning

confidence: 99%

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Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice

Xiao

et al. 2018

Arthritis Res Ther

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BackgroundStudies on the relationship between osteoporosis and intervertebral disc degeneration (IVDD) are inconsistent. Therefore, we assessed whether IVDD is affected by vertebral osteoporosis in ovariectomized mice and investigated the underlying pathogenesis of IVDD related to osteoporosis.MethodsThirty healthy female C57BL/6 J mice aged 8 weeks were randomly divided into two groups: a control group (sham operation, n = 15) and an ovariectomy group (OVX; bilateral ovariectomy, n = 15). At 12 weeks after surgery, the bone quantity and microstructure in the lumbar vertebra and endplate as well as the volume of the L4/5 disc space were evaluated by microcomputed tomography (micro-CT). The occurrence and characteristic alterations of IVDD were identified via histopathological staining. The osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining. Type II collagen (Col II), osterix (OSX), osteopontin (OPN), and vascular endothelial growth factor (VEGF) expression in the intervertebral disc were detected by immunohistochemical analysis.ResultsOVX significantly increased the body weight and decreased the uterus weight. Micro-CT analysis showed that osteoporosis of the vertebra and osteochondral remodeling of the endplate were accompanied by an increase in the endplate porosity and a decrease in the disc volume in the OVX group. Likewise, histological evaluation revealed that IVDD occurred at 12 weeks after ovariectomy, with features of endochondral ossification of the endplate, loose and broken annulus fibrosus, and degeneration of nucleus pulposus. TRAP staining showed that numerous active osteoclasts appeared in the subchondral bone and cartilaginous endplate of OVX mice, whereas osteoclasts were rarely detected in control mice. Immunohistochemical analysis demonstrated that the expression of osterix was significantly increased, notably in the endplate of OVX mice. In addition, Col II was decreased in the ossification endplate and the degenerative annulus fibrosus, where OPN and VEGF expressions were elevated in OVX mice.ConclusionsOVX induced vertebral osteoporosis and osteochondral remodeling of the cartilaginous endplate contributing to the angiogenesis and an increase in porosity of the bone-cartilage surface, and also affected the matrix metabolism which consequently had detrimental effects on the intervertebral disc. Our study suggests that preserving the structural integrity and the function of the adjacent structures, including the vertebrae and endplates, may protect the disc against degeneration.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1701-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice

Xiao

et al. 2018

Arthritis Res Ther

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“…The significant items in the results of enrichment analyses in the present study included 'integrin binding', 'ossification', 'ECM' and 'skeletal system development' Li et al (35) previously reported that the loss of OPG leads to the occurrence of IDD by promoting the 'ossification' biological process of the cartilage endplate in the osteoprotegerin (OPG)-knockout mice. Qu et al (36) reported that DEGs were primarily involved in 'skeletal system development' in a co-expression network in IDD and serve an important role the pathobiology of the disease.…”

Section: Discussionmentioning

confidence: 73%

Comprehensive evaluation of differential long non‑coding RNA and gene expression in patients with cartilaginous endplate degeneration of cervical vertebra

Yuan

Jia

et al. 2020

Exp Ther Med

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Long non-coding RNAs (lncRNAs) are emerging as key regulators in gene expression; however, little is currently known regarding their role in cartilaginous endplate (CE) degeneration (CED) of cervical vertebra. The present study aimed to investigate the expression levels of lncRNAs and analyze their potential functions in CED of cervical vertebra in patients with cervical fracture and cervical spondylosis. Human competitive endogenous RNA (ceRNA) array was used to analyze lncRNA and mRNA expression levels in CE samples from patients with cervical fracture and cervical spondylosis, who received anterior cervical discectomy and fusion. Differentially expressed lncRNAs (DELs) or differentially expressed genes (DEGs) were identified and functionally analyzed, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. An lncRNA-microRNA(miRNA)-mRNA ceRNA regulatory network was constructed based on the DELs and DEGs, and the ceRNA network was visualized using Cytoscape 3.7.2 software. In total, one downregulated mRNA, one upregulated miRNA and five downstream regulated lncRNAs were identified using reverse transcription-quantitative PCR in CED and healthy CE samples. A total of 369 lncRNAs and 246 mRNAs were identified as differentially expressed in CE. The GO and KEGG analyses demonstrated that the majority of GO and KEGG enrichments were associated with CED. Furthermore, a ceRNA network was established, including 168 putative miRNA response elements, 189 upregulated and 37 downregulated lncRNAs and 47 upregulated and 10dow regulated DEGs. The present study analyzed the function of DEGs in the ceRNA network and filtered out the same items as in DEG-function enrichment analysis. These results provide a new perspective for an improved understanding of ceRNA-mediated gene regulation in cervical spondylosis, and provide a novel theoretical basis for further studies on the function of lncRNA in cervical spondylosis. However, further experiments are required to validate the results of the present study.

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“…In this study, the MVD was calculated by counting the CD34-positive vascular endothelial cells in the VEP. Li et al's study 57 suggested that CD34 is a sensitive marker for microvessels in the VEP. Therefore, we believe that although mechanical loading may cause vascular collapse or deformation, the MVD can still be calculated as long as the vascular endothelial cells were preserved.…”

Section: Discussionmentioning

confidence: 99%

Effects of Axial Compression and Distraction on Vascular Bud and VEGFA Expression in the Vertebral Endplate of an Ex Vivo Rabbit Spinal Motion Segment Culture Model

Zhan

Wang²,

Feng³

et al. 2020

Spine

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StudyDesign. An ex vivo study of the rabbit's vertebral endplate.Objective. The aim of this study was to assess the effect of axial compression and distraction on vascular buds and vascular endothelial growth factor (VEGFA) expression of the vertebral endplate (VEP). Summary of Background Data. The abnormal load can lead to intervertebral disc degeneration (IDD), whereas axial distraction can delay this process. The effects of different mechanical loads on the intervertebral disc (IVD) have been hypothesized to be related to changes in the vascular buds of the VEP; moreover, the process that might involve the vascular endothelial growth factor (VEGF) within the VEP. Methods. Rabbit spinal segments (n ¼ 40) were harvested and randomly classified into four groups: Control group, no stress was applied; Group A, a constant compressive load applied; Group B, compression load removed for a fixed time daily on a continuous basis, and substituted with a distraction load for 30 minutes; and Group C, compression removed for 30 minutes for a fixed period daily on a continuous basis. Tissue specimens were collected before the culture (day 0) and on day 14 postculture of each group for analysis of IVDs' morphology, and protein and mRNA expression of Aggrecan, COL2al, VEGFA, and vascular endothelial growth factor receptor 2 of the VEPs. Results. Application of axial distraction and dynamic load compression significantly delayed time-and constant compression-mediated VEP changes and IDD. Moreover, the degree of degeneration was associated with loss of vascular buds, as well as the downregulation of VEGFA and its receptor. Conclusion. The regulation of vascular buds and VEGF expression in the VEP represents one of the mechanisms of axial distraction and dynamic loading.

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Deletion of Opg Leads to Increased Neovascularization and Expression of Inflammatory Cytokines in the Lumbar Intervertebral Disc of Mice

Abstract: N/A.

Cited by 16 publications

References 55 publications

Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice

Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice

Comprehensive evaluation of differential long non‑coding RNA and gene expression in patients with cartilaginous endplate degeneration of cervical vertebra

Effects of Axial Compression and Distraction on Vascular Bud and VEGFA Expression in the Vertebral Endplate of an Ex Vivo Rabbit Spinal Motion Segment Culture Model

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