Canonical Wnt signaling and caveolae play a role in intervertebral disc degeneration; the continuing saga of the mysterious notochordal cell

Abstract

Over the past few decades small animal models mainly involving rodents and rabbits have been developed whereby needle puncture, stab incision or enzymatic approaches have been validated to create the degenerative disc. Although important, these models continue to be plagued by biological attributes that limit applicability to the human condition. However, the fascinating story of two naturally occurring subspecies of canine, the non-chondrodystrophic and chondrodystrophic canine, provides us with an animal model that differentially is protected from the development of degenerative disc disease. Here, Smolders and colleagues provide the first steps to understanding some of the secrets held by man's best friend.

Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/β-catenin pathway activity

“…Subgroup analysis of the three different degeneration degrees showed that axin2 gene expression was significantly higher in chondrodystrophic dogs compared with non-chondrodystrophic dogs. Their findings showed that at the early stage of disc degeneration in dogs, the number of notochord cells decreased, and the number of chondrocyte-like cells increased, along with reduced expression of Wnt/β-catenin, which was consistent with the results of the present and previous studies 45 46 . However, some studies reported that compared with healthy controls, Wnt/β-catenin pathway activity in a degenerated intervertebral disc was up-regulated 48 49 50 .…”

“…Although early processes in disc degeneration have been investigated in histopathology, the biomolecular signal transduction pathways involved in the conversion of notochord cells into chondrocyte-like cells remain unclear 43 44 . Among the many signalling pathways, the Wnt/β-catenin pathway plays an important regulatory role in disc embryonic development and has become a hot spot in disc degeneration in recent years 20 45 46 . Smolders and his colleagues used Dual channel DNA microarrays to compare healthy NP containing only notochord cells (notochord cells-rich), NP with a mixed population of notochord cells and chondrocyte-like cells (Mixed) and NP containing solely chondrocyte-like cells (chondrocyte-like cells-rich) in both non-chondrodystrophic and chondrodystrophic dogs 47 .…”

“…Oestrogen and PTH alleviated disc degeneration via the above three factors and improved the proportion of notochord cells and the activity of the Wnt/β-catenin pathway. Regulating mechanisms of the Wnt/β-catenin pathway in the disc are very complicated, and research has only recently started to focus on these mechanisms and has reported conflicting conclusions 45 46 47 49 50 55 . The present study was performed with female SD rats; the intervention included ovariectomy and oestrogen or PTH replacement, the degeneration time was set to 5 months after ovariectomy, and we studied the Wnt/β-catenin pathway changes during disc degeneration.…”

Characterization of microRNA expression profiles in patients with intervertebral disc degeneration

“…As shown in a previous study, hyperbaric oxygen treatment suppresses the MAPK signaling pathway in degenerated human intervertebral disc cells ( 41 ). In addition, investigators from The Netherlands have used a canine model of IDD to examine the biochemical changes associated with chondroid metaplasia, and found a downreguation of Wnt signaling and caveolin-1 expression ( 42 ). Our results suggest that miRNAs are important regulators of IDD through the modulation of several signaling pathways.…”

CCAAT/enhancer binding protein β regulates the expression of tumor necrosis factor-α in the nucleus pulposus cells

“…Various messengers that act from within the cell to initiate a variety of signaling evens have been identified . Several research groups have also suggested that Wnt signaling plays an important role in IVD degeneration . Furthermore, we have reported the relationship between Tumor Necrosis Factor‐α (TNF‐α) and Wnt signaling in IVD cells .…”