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.
Highlights
Back pain is a global health problem with a considerable socioeconomic burden, and intervertebral disc (IVD) degeneration is one of the major independent risk factors [1].current surgical treatments for IVD degenerative diseases, e.g., pathological disc excision and/or spinal fusion, result in the loss of some spinal function
We compared the expression of extracellular matrix (ECM)-related genes in bovine NP (bNP) cells augmented with
We assessed the histological characteristics of accumulated keratan sulfate (KS) as the specific glycosaminoglycan chain of aggrecan to support the gene expression of aggrecan core protein (Acan)
Summary
Back pain is a global health problem with a considerable socioeconomic burden, and intervertebral disc (IVD) degeneration is one of the major independent risk factors [1].current surgical treatments for IVD degenerative diseases, e.g., pathological disc excision and/or spinal fusion, result in the loss of some spinal function. The development of regenerative therapy has been pursued; its success has been met with such obstacles as avascularity in IVD, lack of regenerative capability of resident cells, and incessant mechanical loading. The IVD is immune-privileged, but is the largest avascular organ in the body [3], which places resident cells in an extremely harsh environment—low glucose, oxygen, and pH and high osmotic pressure (OP) and load repetition [4]. To develop therapeutic strategies for IVD diseases, we have been focusing on the physiological microenvironment and homeostasis within NP. Our latest studies demonstrate that a repetitive regimen of cyclic HP followed by constant HP at high osmolality stimulated anabolic gene upregulation and dense accumulation of ECM in bovine NP (bNP) cells [10,11]. The combination of dynamic HP and intradiscal high OP is required in maintaining bNP-cell homeostasis [10,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
