Age-Related Changes in the Extracellular Matrix of Nucleus Pulposus and Anulus Fibrosus of Human Intervertebral Disc

Abstract

Study Design-To characterize age-related changes in the matrix of human intervertebral disc specimens, human specimens from the 3 rd to the 8 th decade of life were collected and analyzed for collagen and proteoglycan composition.Objectives-To identify age-related changes in the concentration of matrix macromolecules (collagen and proteoglycans, including the small leucine-rich proteoglycans biglycan, decorin, fibromodulin and lumican) in human anulus fibrosus and nucleus pulposus.Summary of Background Data-Intervertebral disc degeneration is associated with changes in the concentration and fragmentation of matrix molecules. Deciphering age-related matrix alterations may help us to better understand the regulatory mechanisms underlying intervertebral disc degeneration.Methods-Forty-six whole intervertebral discs were obtained from the thoracolumbar spines (T11-L5) of humans aged between 32 and 80 years. All specimens were classified as Thompson Grade 1 or 2 according to MRI criteria. Specimens were separated into (i) outer-and (ii) inner anulus fibrosus as well as (iii) nucleus pulposus. DNA, collagen and proteoglycan contents were measured using chemical assays while small non-aggregating proteoglycan levels were analyzed by comparative Western blotting.Results-Total proteoglycan and collagen contents in both the anulus fibrosus and nucleus pulposus consistently decreased with aging. The concentrations of small non-aggregating proteoglycans varied. In the outer anulus, decorin levels decreased while biglycan and fibromodulin levels increased with age. In the inner anulus and nucleus, biglycan demonstrated a significant increase with aging. These changes differed in most cases from those previously reported for degenerating disc tissues.Conclusions-Collagen and proteoglycans appeared to undergo specific age-related changes in the human intervertebral disc. While the total contents of these two families of molecules decreased during aging, individual species of small non-aggregating proteoglycans showed species-specific age-related changes. Interestingly, the level of biglycan rose and remained elevated in all three NIH Public AccessAuthor Manuscript Spine (Phila Pa 1976 compartments of the disc with aging. The functional significance of these alterations is yet to be determined.

Age- and degeneration-related variations in cell density and glycosaminoglycan content in the human cervical intervertebral disc and its endplates

“…Recent years have seen a multitude of studies focusing on the analysis of changes in the extracellular matrix of the IVD during ageing [4,5,7,13,14,15,16,17,18]. However, despite tremendous research efforts, we still lack knowledge regarding cell density and GAG content throughout the IVD.…”

“…However, no such study has been performed in cervical IVDs. As IVD degeneration is driven partially by aging [15], it is not easy to differentiate changes that are a consequence of aging itself from those that develop because of tissue degeneration and the accompanying repair process. Additional research is needed to determine how age and degeneration influence IVD and endplate extracellular matrix composition.…”

“…During IVD degeneration, proteolytic fragmentation of large and small proteoglycans may induce or inhibit essential inflammatory response pathways, altering the ability of the extracellular matrix to maintain its structural integrity [14,15]. Loss of proteoglycans in the NP is a clear sign of early IVD degeneration [16].…”

A comparative evaluation of the small leucine-rich proteoglycans of pathological human intervertebral discs

“…This is responsible for the water retaining and hydrodynamic properties of the extracellular matrix, allowing the composite IVD to act as a weight bearing cushion [33]. Whilst aggrecan is the major IVD PG, there are also small leucine-rich proteoglycans (SLRPs) present, with decorin, biglycan, fibromodulin and lumican all having been reported in the disc [18,29,30].…”

Effects of Initial Boost with TGF-Beta 1 and Grade of Intervertebral Disc Degeneration on 3D Culture of Human Annulus Fibrosus Cells

“…These matrix molecules were shown to have considerably low turnover rates [4,5]. Age and degeneration appear to have distinguishable effects on the AF [6][7][8]. The overall proteoglycan concentration, including the small proteoglycans decorin and biglycan, seem to decrease with age; whereas with degeneration, increased proteoglycan concentrations for moderate and decreased proteoglycan concentrations for severely degenerated AF are reported.…”