Intervertebral Disc Development Is Regulated by Wnt/β-catenin Signaling

Study Design. Histologic analysis of intervertebral disc (IVD) in three types of transgenic mice. Objective. To investigate the role of Wnt/beta-catenin signaling in regulation of IVD development and organization. Summary of Background Data. beta-catenin dependent Wnt signaling is one of the central regulators in cartilage development during limb skeletal formation. Little is known, however, about the physiologic relevance of this signaling pathway to IVD development and organization. Methods. Temporal-spatial distribution of Wnt/beta-catenin signaling activity was examined in IVD using Wnt/beta-catenin reporter (TOPGAL) mice. The structural changes in the mouse IVD components such as the nucleus pulposus (NP), endplate (EP), annulus fibrosus (AF), and the growth plate (GP) of the vertebral body were analyzed after transient activation of Wnt/beta-catenin signaling or deletion of beta-catenin in the mice. Results. Activity of Wnt/beta-catenin signaling was high in EP, AF, and GP in the embryonic stages and decreased at the postnatal stage; it was undetectable in the embryonic NP but upregulated after birth. The transient activation of Wnt/beta-catenin signaling caused severe deterioration of the GP and the AF, whereas deficiency of beta-catenin accelerated bone formation in between EP and GP. Conclusion. The findings in this study suggest that proper regulation of Wnt/beta-catenin signaling is required for development and organization of IVD.