Role of β-catenin signaling in intervertebral disc degeneration: Comment on the article by Wang et al


Role of β-Catenin Signaling in Intervertebral Disc Degeneration: Comment on the Article by Wang et al

To the Editor:

Wang et al confirmed that β-catenin signaling promotes the development of disc disease in β-catenin conditional activation mice (1). The authors found that β-catenin signaling increases disease severity by enhancing levels of matrix metalloproteinase 13 (MMP-13) and ADAMTS-5, indicating that β-catenin signaling plays a major role in intervertebral disc (IVD) function and may contribute to the development of IVD degeneration.

It has been demonstrated that β-catenin is a key molecule in the canonical Wnt signaling pathway for bone regeneration (2). Another study has shown that activation of Wnt/β-catenin promotes cellular senescence and may modulate MMP-9, MMP-10, and transforming growth factor β signaling in nucleus pulposus (3). Smolders et al confirmed that Wnt/β-catenin in notochordal cells is up-regulated in early IVD degeneration (4). In addition, Kondo et al showed that dynamic changes in Wnt/β-catenin occur during IVD development (5). Activity of Wnt/β-catenin is high in end plate, anulus fibrosus, and vertebral body growth plates in the embryonic stages and declines after birth; it is undetectable in the embryonic nucleus pulposus but up-regulated at the postnatal stage. Moreover, transient activation of Wnt/β-catenin results in severe degeneration of the growth plate and the anulus fibrosus, whereas deletion of Wnt/β-catenin in mice promoted bone formation between the end plate and the growth plate. Recently, Hiyama et al demonstrated that activation of Wnt/β-catenin by LiCl, the Wnt/β-catenin activator, results in increased expression of β-catenin, indicating that Wnt/β-catenin signals contribute to the pathogenesis of IVD degeneration (6).

In summary, Wang and colleagues identified a key role of β-catenin activation in disc cells in the development of IVD degeneration. However, the data were obtained using an animal model. To determine the exact mechanisms of β-catenin in IVD degeneration, further studies that include a large sample size and employ rigorous methodology are required, especially in human subjects.

Xia Li PhD*, Qing-Yi Zhao PhD*, Feng-Lai Yuan PhD*, * The Third Hospital Affiliated to Nantong University, Wuxi, Jiangsu, China.