VEGF vascularization pathway in human intervertebral disc does not change during the disc degeneration process

Abstract

ObjectiveDuring degeneration of the intervertebral disc ingrowth of blood vessels and nerves into the disc are associated with back pain. Vascular endothelial growth factors promote vasculogenesis by binding to the membrane vascular endothelial growth factor receptor 1, while shorter soluble forms of this receptor can inhibit vascularization. We hypothesized that membrane and soluble receptor forms might change between stages of intervertebral disc degeneration.ResultsExpression of soluble and membrane forms of vascular endothelial growth factor receptor 1 in human degenerated intervertebral discs and healthy bovine caudal discs was assessed by qRT-PCR and immunoblot. Comparative microarray meta-analysis across disc degeneration grades showed that membrane and soluble forms of this receptor, together with other components of classic vascularization pathways, are constitutively expressed across human disc degeneration stages. Contrary to our hypothesis, we observed that expression of the classic vascularization pathway is stable across degeneration stages and we assume that soluble vascular endothelial growth factor receptor 1 does not contribute to prevent disc degeneration. However, we observed increased expression levels of genes involved in alternative vascularization signalling pathways in severely degenerated discs, suggesting that abnormal vascularization is part of the pathological progression of disc degeneration.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3441-3) contains supplementary material, which is available to authorized users.

Nose to back: compatibility of nasal chondrocytes with environmental conditions mimicking a degenerated intervertebral disc

“…Furthermore, NCs have improved capacity for ECM deposition as compared to AC in articular joint settings (Candrian et al, 2008;Kafienah et al, 2002;Pelttari et al, 2014;Scotti et al, 2012). These findings and many others validating NCs for tissue-engineered cartilage constructs (Asawa et al, 2009;Chia et al, 2005;Fulco et al, 2014;Hellingman et al, 2011;Malda et al, 2004;Reuther et al, 2014;Richmon et al, 2005;Twu et al, 2014;Watson and Reuther, 2014) have aroused the interest to consider NCs for NP tissue regeneration (Tsaryk et al, 2015;Tsaryk et al, 2017).…”

“…In fact, even the most chondrogenic MSCs consistently displayed weakened ability to synthesise ECM the harsher the environment became, up to the point of probable cell death in acidic medium. MSC vulnerability to the environment at the implantation site has been observed in various studies on different tissues (Degano et al, 2008;Haider and Ashraf, 2008;Logeart-Avramoglou et al, 2010;Togel et al, 2008). One of the harshest surroundings is found in the IVD, due to the IVD being the largest non-vascularised structure of the human body.…”

“…This effect, also witnessed in MSC clinical studies for other tissues, is increasingly attributed to the paracrine activity of MSCs, MSCmediated transfer of organelles, as well as the transfer of molecules through MSC-derived extra-cellular vesicles (Spees et al, 2016). These characteristics of MSCs have become so distinguishable to suggest the name of "Medicinal Signalling Cells" (Caplan, 2017). In this regard, the study aim was not to discourage MSC consideration for DDD treatment but imply that direct tissue replacement or regeneration is not to be expected.…”

“…MSCs were isolated and expanded in minimum essential medium alpha modification (αMEM)-based basic medium supplemented with 5 ng/mL FGF2 for a total of two passages, according to an established protocol (Frank et al, 2002;Muller et al, 2009). NP cells were isolated by digestion with 0.05 % type II collagenase for 22 h and resuspended in basic medium using DMEM: nutrient mixture F-12 (DMEM/F12; 21331-046, Gibco) supplemented with 5 ng/mL FGF2, according to the protocol described by Capossela et al (2018). Medium was changed twice a week.…”

“…Lower back pain affects more than 600 million people globally, being the leading disability worldwide (Vos et al, 2012). Intervertebral disc (IVD) degeneration is the most common cause of specific lower back pain (de Schepper et al, 2010;Luoma et al, 2000). The IVD is a symphysis between two vertebral bodies and is the largest non-vascularised structure in the human body.…”