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

Abstract

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.

Herbal Formula Modified Bu-Shen-Huo-Xue Decoction Attenuates Intervertebral Disc Degeneration via Regulating Inflammation and Oxidative Stress

“…Wang et al found that the degeneration of NP cells was ameliorated by regulating the ITGA2/PI3K/Akt signaling pathway [ 47 ]. Moreover, Zhan et al found that the degree of intervertebral disc degeneration was related to the loss of vascular buds and the downregulation of VEGFA and its receptors [ 48 ].…”

Pharmacological Mechanism of Danggui-Sini Formula for Intervertebral Disc Degeneration: A Network Pharmacology Study

“…AKT/PI3K is a key component of many signaling pathways, and AKT proteins regulate a wide variety of cellular functions, including cell proliferation, survival, metabolism, and angiogenesis, in both normal and malignant cells. Moreover, Zhan et al found that the degree of intervertebral disc degeneration was related to the loss of vascular buds and the downregulation of VEGFA and its receptors [ 41 ].…”

New Hope for Treating Intervertebral Disc Degeneration: Microsphere-Based Delivery System

“…Moreover, genetic polymorphism studies may also provide a basis for this, as genetic polymorphisms in inflammatory factors (IL-1α/β, IL-6, and TNF-α), MMPs (MMP-1, -2, -3), collagen (COL), aggrecan (ACAN), and cartilage intermediate proteins may be associated with the pathogenesis of IVDD in populations from several countries ( Mayer et al, 2013 ; Harshitha et al, 2018 ; Trefilova et al, 2021 ). It is well known that both prolonged compression, strain, and acute nonphysiological loading acting on the IVD can lead to a range of changes, such as tissue damage, reduced vascular buds, decreased cellular activity, inflammatory factor release, and ECM degradation ( Alkhatib et al, 2014 ; Zhan et al, 2020 ; Zhan et al, 2021 ; Zhou et al, 2021 ), which ultimately result in IVDD. Disregarding exogenous factors, the IVD is a hypoxic, low nutrient acidic microenvironment due to the absence of blood supply ( Bibby et al, 2005 ).…”