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Review
. 2011;21(1):29-41.
doi: 10.1615/critreveukargeneexpr.v21.i1.30.

Notochordal cells in the adult intervertebral disc: new perspective on an old question

Makarand V Risbud  1 , Irving M Shapiro
Affiliations
Review

Notochordal cells in the adult intervertebral disc: new perspective on an old question

Makarand V Risbud et al. Crit Rev Eukaryot Gene Expr. 2011.

Abstract

The intervertebral disc is a tissue positioned between each of the vertebrae that accommodates applied biomechanical forces to the spine. The central compartment of the disc contains the nucleus pulposus (NP) which is enclosed by the annulus fibrosus and the endplate cartilage.The NP is derived from the notochord, a rod-like structure of mesodermal origin. Development of the notochord is tightly regulated by interactive transcription factors and target genes. Since a number of these molecules are unique they have be used for cell lineage and fate mapping studies of tissues of the intervertebral disc. These studies have shown that in a number of species including human, NP tissue retains notochordal cells throughout life. In the adult NP, there are present both large and small notochordal cells, as well as a progenitor cell population which can differentiate along the mesengenic pathway. Since tissue renewal in the intervertebral disc is dependent on the ability of these cells to commit to the NP lineage and undergo terminal differentiation, studies have been performed to assess which signaling pathways may regulate these activities. The notch signaling pathway is active in the intervertebral disc and is responsive to hypoxia, probably through HIF-1a. From a disease viewpoint, it is hypothesized that an oxemic shift, possibly mediated by alterations in the vascular supply to the tissues of the disc would be expected to lead to a failure in notochordal progenitor cell activation and a decrease in the number of differentiated cells. In turn, this would lead to decrements in function and enhancement of the effect of agents that are known to promote disc degeneration.

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Figures

FIGURE 1
FIGURE 1
A saggital section through neonatal (A) and mature (B) rat intervertebral disc showing the nucleus pulposus (NP), annulus fibrosus (AF), and endplate cartilage (EP). Note that in the neonate, the NP is highly cellular containing large vacuolated notochordal cells and there is little deposition of extracellular proteoglycan matrix. At this stage the sclerotomal-derived EP and AF are not completely organized and endochondral ossification of the vertebrae is yet to occur. Original Mag. X10. In the adult NP, the ratio of proteoglycan matrix to cells is high. The AF exhibits a characteristic lamellar structure in the adult. Original Mag. X4.
FIGURE 2
FIGURE 2
(A) During segmentation the paraxial mesoderm forms pairs of somites along the neural tube (light orange) and notochord (blue). Each somite is composed of a dermatome (light purple), myotome (light brown), and sclerotome (dark yellow). The ectoderm lies above and the endoderm below. (B) Sclerotomal cells migrate from adjacent somites above and below each future vertebra. Dermatomal cells stream beneath the ectoderm to form the dermis, while the myotomal cells form muscle. Insert B shows the architecture of the vertebrae with the spinal canal, spinal processes, and the nucleus pulposus in blue. Courtesy of Dr. Richard Dryden.
FIGURE 3
FIGURE 3
Brachyury expression in cells of the nucleus pulposus. A) Low magnification saggital section of the E15.5 mouse embryo showing brachyury staining in the developing nucleus pulposus. Note that the annulus fibrosus and endplate cartilage is negative (10X). B) High magnification image of the developing nucleus pulposus that is shown by an arrow in panel A (20X). All cells show intense nuclear staining of brachyury. C) Western blot analysis of brachyury expression in nucleus pulposus tissue isolated from progressively degenerate human discs (Thompson Grade II–V). A robust expression of brachyury was seen in all the nucleus pulposus samples. Reproduced with permission.
FIGURE 4
FIGURE 4
Schematic indicating current theories concerning the origin of cells of the nucleus pulposus (NP). Although it is well established that the notochord (NC) gives rise to large NP cells during embryogenesis, there is discord concerning the origin of small chondrocytic cells in the adult disc. As the NC contains both small spindle-shaped cells as well as large vacuolated cells, we hypothesize that both the large vacuolated cells (LVC) and chondrocyte-like cells (CLC) of the NP are derived from the notochord. These cells then undergo self renewal to maintain cellular homeostasis of the NP tissue. It is possible that LVC may differentiate into CLC. It is known that the perinotochordal sheath (PNS) gives rise to both endplate (EP) chondrocytes and annulus fibrosus (AF) cells. Some researchers are of the opinion that in the adult, endplate chondrocytes and inner annulus fibrosus cells give rise to CLC at the same time replacing LVC. There is debate that loss or replacement of LVC in the nucleus pulposus initiates disc degeneration. Reproduced with permission.
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