Role of Sonic Hedgehog Signaling Pathway in Intervertebral Disc Formation and Maintenance

Abstract

A purpose of review: The intervertebral discs (IVD) are an essential component of the spine. Degeneration of the discs, commonly due to age or injury, is a leading cause of chronic lower back pain. Despite its high prevalence, there is no effective treatment for disc disease due to limited understanding of disc at the cellular and molecular level.

B recent findings: Recent research has demonstrated the importance of the intracellular developmental pathway sonic hedgehog (Shh) during the formation and postnatal maintenance of the IVD. Recent studies corroborate that the down-regulation of SHH expression is associated with pathological changes in the IVDs and demonstrate the reactivation of the hedgehog pathway as a promising avenue for rescuing health disc structure and function.

C summary: Understanding the role of developmental signaling pathways that regulate disc formation and maintenance may help develop strategies to recapitulate the same mechanism for disc treatment and hence improve the quality and longevity of patient lives.

Keywords: Brachyury; Sonic hedgehog signaling; disc therapy; intervertebral disc degeneration; intervertebral disc development; intervertebral disc regeneration.

Figure 1.

Hematoxylin and Eosin stained mid-coronal sections of lumbar intervertebral disc from one-week-old (A) and one-year-old mice show age-related structural changes. In the young, healthy disc, the Hh signaling pathway is turned on by Shh ligand produced by NP cells, resulting in the activation of the signal transduction pathway as illustrated in (C). Shh expression reduces in NP cells with age, and thus the Hh signaling pathway in (B) would be turned off, as shown in (D). Scale bar in (A) and (B) is 200 µm. NP=nucleus pulposus; AF=annulus fibrosus; EP=end plate