The role of extracellular matrix elasticity and composition in regulating the nucleus pulposus cell phenotype in the intervertebral disc: a narrative review.

The intervertebral disc (IVD) is a heterogeneous, fibrocartilaginous tissue that provides load support, energy dissipation, and flexibility in the spine. The IVD, which is composed of the nucleus pulposus (NP), anulus fibrosus (AF), and cartilage endplate (Fig. ​(Fig.1),1), is situated between adjacent vertebral bodies and acts as the main joint of the spinal column, occupying approximately 1/3 of its total height [1,2]. The cells within each of the regions of the IVD are subjected to a variety of signals from both physical and biochemical stimuli from their surrounding extracellular matrix (ECM) microenvironment [3–8]. These cues are believed to play critical roles in regulating development, maintenance, and repair of the IVD, but in ways that are poorly understood. Fig. 1 The intervertebral disc is situated between vertebral bodies in the spinal column, and acts to support loads, provide flexibility, and dissipate energy in the spine. The disc is comprised of distinct anatomic zones: the anulus fibrosus (AF), nucleus pulposus ... During disc degeneration or aging, significant changes are observed in IVD cell phenotype and density in parallel with changes in ECM composition and structure. A dramatic decrease in cell density and multicell clusters in both the NP and AF regions is observed [9–11] with increased prevalence of cells with cytoplasmic projections [12–14]. While the exact factors resulting in decreased NP cell clustering with age in vivo are not fully understood, it is likely that cell death associated with decreased nutrient oxygen and glucose transport to the IVD can contribute to these decreased cell numbers and cell clusters [2]. With decreases in cell density, the large, vacuolated cells in the NP, which are normally arranged in cell clusters, transition to a sparse population of smaller, isolated chondrocyte-like cells [15]. The loss of proteoglycan matrix causes changes in proteoglycan structure [16–18], which results in decreased negative fixed-charge density, decreased water content, and a loss of swelling pressure [19,20], impairing the tissue's ability to resist and redistribute compressive loads. Corresponding with these compositional changes are structural alterations including loss of disc height and increased anulus lamellar disorganization. Changes in ECM composition and structure may also result in substantially altered mechanics and kinematics for the entire IVD motion segment, with decreased internal pressurization and disc height resulting in higher compressive loads transferred to the AF, compromising its structure and function (e.g., overload leading to clefts, buckling, or rupture). Nerve compression, spinal canal impingement, and altered spinal loading configurations can also occur, which can contribute to symptomatic back pain [21]. These dramatic shifts in ECM mechanical environment can be expected to impact NP cell health, metabolism and survival, although the direct links between environmental factors and NP cell behaviors are still under study. The purpose of this article is to review our experience with studies of NP cell interactions with their surrounding ECM, as this knowledge can be useful in the development of treatments for disc-related ailments. The first section of this article covers what we have learned of how NP cells interact with select proteins of the native ECM. We then describe how changes in the surrounding ECM can alter NP cell phenotype and morphology, and summarize recent work performed to reveal how NP cells sense, interpret, and respond to different mechanical and biochemical cues in their ECM.