Augmented Chondroitin Sulfate Proteoglycan Has Therapeutic Potential for Intervertebral Disc Degeneration by Stimulating Anabolic Turnover in Bovine Nucleus Pulposus Cells under Changes in Hydrostatic Pressure

Abstract

Nucleus pulposus (NP) cells are exposed to changes in hydrostatic pressure (HP) and osmotic pressure within the intervertebral disc. We focused on main disc matrix components, chondroitin sulfate proteoglycan (CSPG) and hyaluronan (HA) to elucidate the capability of augmented CSPG to enhance the anabolism of bovine NP (bNP) cells under repetitive changes in HP at high osmolality. Aggrecan expression with CSPG in the absence of HP was significantly upregulated compared to the no-material control (phosphate buffer saline) under no HP at 3 days, and aggrecan expression with CSPG under HP was significantly higher than the control with HA under HP at 12 days. Collagen type I expression under no HP was significantly lower with CSPG than in controls at 3 days. Although matrix metalloproteinase 13 expression under HP was downregulated compared to no HP, it was significantly greater with HA than the control and CSPG, even under HP. Immunohistology revealed the involvement of mechanoreceptor of transient receptor potential vanilloid-4 activation under HP, suggesting an HP transduction mechanism. Addition of CSPG had anabolic and anti-fibrotic effects on bNP cells during the early culture period under no HP; furthermore, it showed synergy with dynamic HP to increase bNP-cell anabolism at later time points.

Regenerative Capability of Human Nucleus Pulposus Cells in Degenerated Disc under Hydrostatic Pressure Mimicking Physiologically Relevant Intradiscal Pressure in Vitro

“…These biomarkers were analyzed along with the age of the subjects, cell origin in the cervical or lumbar spine, and degenerative grades of IVD. In addition, we confirmed the effects of HP through the transient receptor potential vanilloid 4 (TRPV4) immunohistologically 9–11…”

“…In addition, we confirmed the effects of HP through the transient receptor potential vanilloid 4 (TRPV4) immunohistologically. [9][10][11]…”

Concepts of Regeneration for Spinal Diseases in 2021

“…Takeoka Y et al [5] studied bovine tail disc NP cells incubated with chondroitin sulfate proteoglycan or hyaluronan under hydrostatic pressure mimicking spinal motion. Chondroitin sulfate proteoglycan had anabolic effects on cells combined with hydrostatic pressure, which could be a potential therapeutic and regenerative scaffold for degenerative disc disease.…”

Elastic Fibers in the Intervertebral Disc: From Form to Function and toward Regeneration

“…This may apply a higher load to the IVD components, cause local stress concentrations, develop tissue clefts, and increase the risk of endplate fracture or IVD failure. The role that different ECM constituents such as collagen and proteoglycans play during the IVD degeneration process has been extensively studied [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]; however, the effect of elastic fibers on the degeneration process and whether they stimulate the biological mechanisms are yet to be explored. Over the past decade, an increasing number of studies have been devoted to the IVD elastic fibers, which has enhanced our understanding of their structural organization and function.…”