I. Intervertebral disk

A. Cells

1. Notochordal cells present embryologically disappear by adult life

2. Chondrocyte-like cells in the nucleus pulposus and annulus fibrosus most likely originate from chondrocytes in the cartilaginous end plate.

3. No significant cell turnover

4. Apoptosis with aging and disk degeneration

c. Provide tensile strength

d. Collagen cross-linking by covalent bonds via modification of lysine/hydroxylysine residues

e. Highest concentration of cross-linking in nucleus

D. Disk degeneration

1. Collagen synthesis and content increase in the nucleus

2. Decreased concentration of cross-linking in the annulus

E. Proteoglycans (PGs)

1. PG aggregates’ constituents

a. Central hyaluronan filament

b. Link proteins attach multiple glycosoaminoglycan molecules

c. Large PGs

(1) Aggrecan

(a) Similar to articular cartilage

(b) Half the size of PGs found in cartilage

(c) Higher keratin sulfate:chondroitin sulfate ratio

(d) Higher molecular weights of keratin sulfate

(e) Increased hyaluron content

(f) Important in water retention

(g) Provides compressive strength

d. Small PGs

(1) Biglycan, decorin, lumican, fibromodulin

(2) Involved in organization of collagen and fibril formation

(3) PG content and synthesis vary depending on age, region, and degeneration.

(4) PG synthetic activity of adult normal annulus approximately one third lower than articular cartilage and young nucleus

(5) Synthetic activity greatest in the inner annulus