|
Natin N. Bhatia, MD
Jeffrey C. Wang, MD ABSTRACT The human nucleus pulposis (NP) is
made of a cellular component, and an extracellular matrix (ECM), which is
mostly type II collagen and proteoglycans, the most common, which is
aggrecan. These proteoglycans
are hydrophilic and serve to retain fluid within the disc.
With aging, the types, proportions of collagen and proteoglycans
change, and clefts/tears develop in the matrix.
It has been shown that with degeneration, the collagen fibrils
widen, fibrous long-spacing collagen and irregular fibril diameters occur,
all evidence of apoptosis. Of the PG’s, aggrecan is the most
important. Studies have shown
that with disc degeneration, the amounts of this product are reduced, but
there is evidence of increased mRNA trying to improve the content of PG.
This phenomenon occurs until the end stage process of degeneration,
and also does not appear to occur in the annulus, only the nucleus.
The annulus fibrosis (AF) is made
mostly of type I collagen, with smaller amounts of types II and III.
It serves to contain the nucleus and bind the vertebrae together.
It permits motion in multiple planes while resisting compressive
forces. With aging, the
organized collagen bundles become more irregular, and the interface
between the annulus and nucleus becomes less defined. Another process that has been found
to occur involves further destruction via a variety of proteolytic
pathways, degraded by specific enzymes such as the metalloproteinases and
cathespsins. These enzymes
break down collagen and proteoglycans, and are found in increasing amounts
in degenerative discs. Other recent studies have shown
that the cells of the NP have a chondrocyte appearance.
They express Sox9, type II collagen, and aggrecan, which are three
markers classically expressed by chondrocytes, and are not found in the
AF. The cells produce less
collagen and aggrecan during the disc degeneration process. Immunohistochemical studies have
found the CD68 antigen, which is a reliable marker for phagocytotic cells,
and is found only in cells with active degeneration. Also, S100 protein has been found, which is a chondrocyte
marker that indicates resident cells might be undergoing phenotypic
conversion and expressing themselves as having phagocyte qualities. Blood supply has been shown to
affect disc viability, and the cells in the middle of the NP may be as far
as 8mm from the nearest blood supply, and have to receive their nutrition
on diffusion from capillaries at the adjacent endplates. The disc survival and matrix production are sensitive to
fluctuations in the nutrient supply, and the increased metabolic demands
from abnormal stress may tax the limited nutrient supply and cause harm to
the discs COMMENTS A nice overview of the current
literature and thinking regarding the disc and the factors that affect its
degeneration. As one can see,
not only mechanical factors as we physical therapists always look at, but
also biohistochemical and genetic factors also.
As with other studies I have covered, the disc has no true blood
supply, and smoking causes small vessel constriction and thus loss of the
diffusion of nutrients. Also,
persons with compromised cardiovascular systems will not have the same
blood flow as those with excellent cardio systems (after all, how many
marathon runners do we treat with chronic disc problems versus overweight,
sedentary smokers?)
|