Abstract
BackgroundThe degeneration of the intervertebral disc (IVD) is characterized by proteolytic degradation of the extracellular matrix, and its repair requires the production of an extracellular matrix with a high proteoglycan-to-collagen ratio characteristic of a nucleus pulposus (NP)-like phenotype in vivo. At the moment, there is no medical treatment to reverse or even retard disc degeneration. The purpose of the present study was to determine if a low dose of short link N (sLN), a recently discovered fragment of the link N peptide, could behave in a manner similar to that of link N in restoring the proteoglycan content and proteoglycan-to-collagen ratio of the disc in a rabbit model of IVD degeneration, as an indication of its potential therapeutic benefit in reversing disc degeneration.MethodsAdolescent New Zealand white rabbits received an annular puncture with an 18-gauge needle into two noncontiguous discs to induce disc degeneration. Two weeks later, either saline (10 μL) or sLN (25 μg in 10 μL saline) was injected into the center of the NP. The sLN concentration was empirically chosen at a lower molar concentration equivalent to half that of link N (100 μg in 10 μL). The effect on radiographic, biochemical and histologic changes were evaluated.ResultsFollowing needle puncture, disc height decreased by about 25–30% within 2 weeks and maintained this loss for the duration of the 12-week study; a single 25-μg sLN injection at 2 weeks partially restored this loss in disc height. sLN injection led to an increase in glycosaminoglycans (GAG) content 12 weeks post-injection in both the NP and annulus fibrosus (AF). There was a trend towards maintaining control disc collagen-content with sLN supplementation and the GAG-to-collagen ratio in the NP was increased when compared to the saline group.ConclusionsWhen administered to the degenerative disc in vivo, sLN injection leads to an increase in proteoglycan content and a trend towards maintaining control disc collagen content in both the NP and AF. This is similar to link N when it is administered to the degenerative disc. Thus, pharmacologically, sLN supplementation could be a novel therapeutic approach for treating disc degeneration.
Highlights
The degeneration of the intervertebral disc (IVD) is characterized by proteolytic degradation of the extracellular matrix, and its repair requires the production of an extracellular matrix with a high proteoglycan-tocollagen ratio characteristic of a nucleus pulposus (NP)-like phenotype in vivo
A single 25-μg short link N (sLN) injection appeared to begin reversing the loss of disc height during the first 2 weeks, and by week 4 the mean normalized %Disc height index (DHI) of injected discs in the sLN group was statistically higher than that in the saline group
GAG concentration was measured in the discs because of the major role proteoglycans play in the functional ability of IVDs to swell and resist compressive forces [38]
Summary
The degeneration of the intervertebral disc (IVD) is characterized by proteolytic degradation of the extracellular matrix, and its repair requires the production of an extracellular matrix with a high proteoglycan-tocollagen ratio characteristic of a nucleus pulposus (NP)-like phenotype in vivo. At later stages of degeneration, the collagen fibrils of the NP become damaged, leading to the formation of clefts that eventually affect the AF. This degeneration of IVD structure and function is a progressive condition and presents a major socioeconomic burden worldwide because of its strong association with back pain. The Twin Spine Study has recently suggested that IVD degeneration may be due, in large part, to genetically determined “developmental” changes in disc structure [25]
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