Research into IVD Cell Mechanobiology and the Role of Genetics in IVD Degeneration Necessary

Role of Genetics in IVD Degeneration

A review 1  of how biochemical and micromechanical events affect the cellular biology and morphology of intravertebral discs (IVD) during physical motion, loading, and compression determined that important interactions between the nucleus pulposus and annular fibrosis altered cells, micromechanical, mechanobiological, and mechanical features. Because previous studies have indicated a strong genetic link in the propensity for disc degeneration, the authors concluded that more information is needed on how these integral biochemical and micromechanical processes may be triggered by genetic factors and contribute to IVD degeneration, annular tears, and endplate or facet damage that can reduce disc height and flexibility, fluid pressurization, and cause stiffness or dissipation of the disc.

 

An Examination of the Intervertebral Disc

The authors of the review emphasized that the three separate anatomic structures of the IVD—namely, the annulus fibrosis, nucleus pulposus, and cartilage endplates, which regulate waste and nutrients and may help pressurize fluids—work together to make the IVD function mechanically.

Negative charges in the gelatinous nucleus pulposus, which is made up of mostly water, glycosomino-glycans, collagens, and other proteins—contribute to pressure and swelling, which helps support spinal loads and distribute forces evenly throughout the annulus fibrosis—a lamellar structure made up of bundles of collagen fibers that help control the tension and stiffness in axial, circumferential, and radial directions during physiologic joint motions.

Pathologic changes in the biochemistry and structure of the extracellular matrix may involve a loss of hydration, decrease in disc height and cell density, disorganization of the lamellar annulus, loss of proteoglycan content, changes in the levels or activity of matrix metalloproteinase, and changes in the proteoglycan structure, leading to degeneration or loss of the negative charge’s fixed density and the swelling pressure that is necessary to assist in spinal loading.

 

Genetic Influence on Degeneration and Cell Morphology

The authors of the review stated that there is much evidence to support the theory that disc degeneration could be genetically-influenced, but emphasized that other factors—including heavy lifting, impact, gait, lifestyle factors, posture, and muscle use— may also be involved in altering the biochemical and mechanical processes within the IVD. Those who are genetically predisposed may be more at risk of disc degeneration triggered by the biochemical and cellular responses to mechanical factors.

 

Intervertebral Cell Morphology

Compressive conditions, tensile stretching, strains, and stresses are all physiologic conditions that contribute to the electro-kinetic, fluid flows, hydrostatic, and osmotic effects of intervertebral disc cell responses.  In adults, the nucleus pulposus is filled with chondrocyte-like cells that may have traversed the endplate or inner annulus fibrosis into the nucleus. Studies have demonstrated that these cells –particularly the innermost cells—contain vimentin filaments that are frequently associated with articular cartilage and other tissues enduring compression. The morphology of examined fibroblast and chondrocyte cells indicate that they are ellipsoidal and contain long axes that are in line with the lamellas’ collagen fibers. Alternatively, the cells normally found in the annulus fibrosis are rounder, with more space in between, and may be surrounded by a type of collagen called chondron.

When IVD degeneration is present, other types of cells are found within the nucleus pulposus, including Schwann cells, nerve fibers, fibroblasts, and endothelial cells. There is also an increase in vasculature –and hydraulic permeability of fluids and proteoglycan contents—associated with the proliferation of array of cells. These factors create electro kinetic effects in the regulation of ion and water movement, as well as the cells’ abilities to send signals to the unit in response to mechanical loading. Similar changes in the annulus fibrosis may be responsible for many of the overt alterations observed in IVD degeneration because of the dependence of the unit upon tissue hydration and negative charge to regulate complex interchanges.

 

Other Changes Noted in IVD Degeneration

High levels of hydrostatic pressure occur with the cells of the IVD during resting and loading. Pressure levels higher or lower than average may inhibit proteoglycan synthesis and create an increase of nitric oxide and MMP-3 production. The cells of the nucleus pulposus and inner annulus fibrosis may be affected by compression, but there is little research to support or disclaim this theory. In addition to fluid movement and mechanically-induced disruptions within the IVD, iron concentrates, Ph, osmolarity, and extracellular hydration also occur.

Many loading conditions may contribute to tensile strains within the IVD. These may include a decrease in the proteoglycan and type 1 and 2 collagen content. High-frequency vibration may increase the release of ATP in the annulus fibrosis cells, and type 3 collagen may be decreased after prolonged exposure to vibration. Studies indicate the release of ATP may help modulate the response to vibration and other mechanical stimuli within the disc cell.

 

Conclusion

Studies of IVD suggest anabolic and catabolic consequences of mechanical stimuli. These responses vary between the inner annulus fibrosis and nucleus pulposus, with higher catabolic responses being evident under significant loading stress and lower magnitude responses occurring with static compression, hydrostatic or osmotic pressures. The studies also suggest a connection between the physiologic range of stimuli and micromechanical consequences that promote cellular repair. These signaling mechanisms, though not sufficiently understood, may involve intracellular Ca transients, remodeling, and ATP release, which act as second messengers to the IVD cells and help regulate genetic expression and subsequent biosynthesis.

Future studies are necessary to fully understand the biologic and chemical signaling devices that serve to regulate the IVD response to mechanical and micromechanical stimuli, as well as the evidently important interactions between genetics, mechanical stresses, cytokines, and the inflammatory responses that appear to play a part in IVD degeneration.

Summary
IVD Cell Mechanobiology the Role Genetics in IVD Degeneration
Article Name
IVD Cell Mechanobiology the Role Genetics in IVD Degeneration
Description
Important interactions between genetics, mechanical stresses, cytokines, and the inflammatory responses that appear to play a part in IVD degeneration.
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Publisher Name
Dynamic Disc Designs
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