The enigma that is the nucleus pulposus cell: the search goes on

Abstract

The development of an effective treatment for degenerative disc disease has been hampered for many years by what seems a fundamental problem; what exactly defines a nucleus pulposus (NP) cell? The paper by Gilson and colleagues elegantly re-opens the debate concerning the lineage and identity of NP cells that are alike yet different from chondrocytes. As we pursue novel investigations and treatment strategies for degenerative disc disease, how do we isolate these unique cells and what is the role of the primordial notochordal cell that may well linger within the NP far longer and perhaps in a different phenotypic appearance than previously thought? The paper by Gilson and colleagues that is the subject of the present editorial presents compelling data concerning the heterogeneity of the cells of the NP, and their origin, development, maturation and function.

The evolutionary importance of cell ratio between notochordal and nucleus pulposus cells: an experimental 3-D co-culture study

“…The fact that the co-culture with cross-specific additional NPCs cells can trigger aggrecan and col 2 gene expression seems to point toward a progenitor-like status of notochordal cells. Moreover, these cells might be of key importance for the regeneration of the intervertebral disc using cell-based approaches [8,13]. Although these notochord cells seem to be highly related to chondrocyte-like cells, the differential response in our co-culture experiments questions whether notochordal cells are irrelevant for the choice of animal models for disc regeneration [30,35].…”

Canonical Wnt signaling in the notochordal cell is upregulated in early intervertebral disk degeneration

“…1). 4,7,10 Thus, the disappearance of NCs accompanied by the appearance of the CLCs seems to be associated with IVD degeneration. 7,10 Canonical Wnt signaling plays a critical role in promoting the differentiation or maintenance of stem cells in a self-renewing state, 11 and sustained Wnt/bcatenin signaling is required to maintain the notochord fate of progenitor cells throughout embryogenesis.…”

“…3 However, much remains enigmatic about IVD progenitor cells and the pathways involved in degeneration. 4,5 The center of the IVD, the nucleus pulposus (NP), is derived from the notochord, 6 and notochordal cells (NCs) are considered potential NP progenitor cells. 4,5 In young humans and in many other species, NCs are the predominant cell type in the NP; however, in some species, such as dogs and humans, the NCs are eventually replaced by smaller, chondrocyte-like cells (CLCs).…”

“…4,5 The center of the IVD, the nucleus pulposus (NP), is derived from the notochord, 6 and notochordal cells (NCs) are considered potential NP progenitor cells. 4,5 In young humans and in many other species, NCs are the predominant cell type in the NP; however, in some species, such as dogs and humans, the NCs are eventually replaced by smaller, chondrocyte-like cells (CLCs). 4,7,8 Dogs suffer from spontaneous IVD degeneration, and the degenerative process involves macroscopic, histopathological, and biochemical changes similar to humans.…”

“…4,5 In young humans and in many other species, NCs are the predominant cell type in the NP; however, in some species, such as dogs and humans, the NCs are eventually replaced by smaller, chondrocyte-like cells (CLCs). 4,7,8 Dogs suffer from spontaneous IVD degeneration, and the degenerative process involves macroscopic, histopathological, and biochemical changes similar to humans. 9 However, the dog is a unique species with regard to NC maintenance and IVD degeneration: chondrodystrophic dog breeds (with disproportionally short limbs relative to the length of the spine) are predisposed to early onset IVD degeneration.…”