Heparanase isoform expression and extracellular matrix remodeling in intervertebral disc degenerative disease

Abstract

OBJECTIVE:To determine the molecules involved in extracellular matrix remodeling and to identify and quantify heparanase isoforms present in herniated and degenerative discs.INTRODUCTION:Heparanase is an endo-beta-glucuronidase that specifically acts upon the heparan sulfate chains of proteoglycans. However, heparanase expression in degenerative intervertebral discs has not yet been evaluated. Notably, previous studies demonstrated a correlation between changes in the heparan sulfate proteoglycan pattern and the degenerative process associated with intervertebral discs.METHODS:Twenty-nine samples of intervertebral degenerative discs, 23 samples of herniated discs and 12 samples of non-degenerative discs were analyzed. The expression of both heparanase isoforms (heparanase-1 and heparanase-2) was evaluated using immunohistochemistry and real-time RT-PCR analysis.RESULTS:Heparanase-1 and heparanase-2 expression levels were significantly higher in the herniated and degenerative discs in comparison to the control tissues, suggesting a possible role of these proteins in the intervertebral degenerative process.CONCLUSION:The overexpression of heparanase isoforms in the degenerative intervertebral discs and the herniated discs suggests a potential role of both proteins in the mediation of inflammatory processes and in extracellular matrix remodeling. The heparanase-2 isoform may be involved in normal metabolic processes, as evidenced by its higher expression in the control intervertebral discs relative to the expression of heparanase-1.

A Global Pictorial Assessment of the Intervertebral Disc Cell in Several Species Reveals a Remarkable Biodiversity in this Cell Type which should be taken into Account in Experimental Studies on Intervertebral Disc Repair

“…Heparanase 1 and 2 expression are elevated in disc degeneration and promote angiogenic wound repair [54]. Heparanase 1 and 2 are produced by osteoblasts these degrade growth plate perlecan releasing HS bound growth factors such as FGF-2 which promote angiogenic processes and bone formation [55,56]. Future research may delineate further the role of glycan depolymerising enzymes in ECM remodeling in health and disease.…”

[ARTIGO RETRATADO] Revisão dos artigos sobre ortopedia recentemente publicados na imprensa científica brasileira

“…Their findings suggest that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis in part through the Src-PLCγ1-MEK1/2-ERK1/2 signaling pathway, which links these three important signaling molecules into a mitogenic cascade. Rodrigues et al 21 studied molecules involved in extracellular matrix remodeling in order to identify and quantify heparanase isoforms present in herniated and degenerative discs.They find that the overexpression of heparanase isoforms in the degenerative intervertebral discs and the herniated discs suggests a potential role of both proteins in the mediation of inflammatory processes and in extracellular matrix remodeling. The heparanase-2 isoform may be involved in normal metabolic processes, as evidenced by its higher expression in the control intervertebral discs relative to the expression of heparanase-1.…”

Expression of matrix factors in the process of neovascularization of intervertebral disc

“…[1][2][3] IDD is associated with pathological conditions of the vertebra, including spinal canal stenosis, foraminal stenosis and spinal disc herniation, often resulting in pain and/or neurological deficit and, ultimately, functional impairment. 4,5 Intervertebral discs (IVDs), which are fibrocartilaginous structures located between the vertebral bodies, are responsible for the absorption, distribution and transmission of loads in the spinal column. They are macroscopically composed of annuli fibrosi (AFs), rich in type 1 collagen, and nucleus pulposus (NP), composed primarily of type 2 collagen and hydrophilic proteoglycans in a complex structure that includes cells, extracellular matrix (ECM) and 70% water.…”