The embryonic and evolutionary boundaries between notochord and cartilage: a new look at nucleus pulposus-specific markers

Abstract

The adult nucleus pulposus (NP) and articular cartilage are similar in terms of their histocytological components and biomechanical functionalities, requiring a deep understanding of NP-specific markers to better evaluate stem-cell-based NP regeneration. Here, we seek to distinguish NP cells from articular chondrocytes (ACs), focusing on differences in their embryonic formation and evolutionary origin. Embryonically, NP cells are conservatively derived from the axial notochord, whereas ACs originate in a diversified manner from paraxial mesoderm and neural crest cells. Evolutionarily, although the origins of vertebrate NP and AC cells can be traced to similar structures within protostomia-like bilaterian ancestors, the distant phylogenetic relationship between the two groups of animals and the differences in the bodily origins of the tissues suggest that the tissues may in fact have undergone parallel evolution within the protostomia and deuterostomia. The numbers of supposedly NP-specific markers are increasing gradually as microarray studies proceed, but no final consensus has been attained on the specificity and physiology of "exclusive" NP markers because of innate variations among species; intrinsic expression of genes that destabilize the circadian clock; and cooperation by, and crosstalk among, different genes in terms of physiology-related phenotypes. We highlight the embryonic and evolutionary boundaries between NP and AC cells, to aid in recognition of the challenges associated with evaluation of the role played by nucleopulpogenic differentiation during stem-cell-based intervertebral disc regeneration.

Normal aging in human lumbar discs: An ultrastructural comparison

“…This insertion is thought to confer additional resistance to shearing and rotational stresses[27]. Our results also demonstrate the absence of these insertions in the NP and is not surprising given the distinct embryological origins[30,31].…”

Directed Differentiation of Notochord-like and Nucleus Pulposus-like Cells Using Human Pluripotent Stem Cells

“…Expression of ARID5B, PHF2, and SOX9 were all significantly increased in the derived cells (FDR q = 1.0 3 10 À32 , 0.003, and 5.9 3 10 À5 , respectively). These and the upregulation of COL2A1 (21.5 times; FDR q = 2.4 3 10 À28 ) may reflect the shared gene expression between CLCs and NCLs (such as SOX9, COL2A1, COL9A2, COL11A1, ACAN, SOX5, and SOX6) (Wang et al, 2018a). Since NCLs (evidenced by T and KRTs; Figure 4A) and CLCs are the two morphologically distinct cell that populate the young/healthy human NP (Risbud et al, 2015), these results show that our protocol for generating hPSCderived NP-like cells is effective, and may produce cells resembling both NCLs and CLCs.…”

Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells

“…Moreover, although the number of suggested NP and AF phenotypic markers is gradually increasing as microarray studies are conducted, no final standards have been reached regarding the specificity of NP and AF markers (Pattappa et al, 2012;Wang et al, 2018a). These limitations greatly obstruct the specific detection of seeded cell differentiation along NP-/AFlike lineages.…”