Notochordal and nucleus pulposus marker expression is maintained by sub-populations of adult human nucleus pulposus cells through aging and degeneration

Abstract

The nucleus pulposus (NP) of the intervertebral disc (IVD) demonstrates substantial changes in cellApproximately 70% of individuals in developed societies suffer from low back pain (LBP) and neck pain at some point 1, 2 . The socioeconomic impact of LBP amounts to over £12 billion in the UK alone 3 , and whilst the underlying pathologies of these are multifactorial, degeneration of the lumbar and cervical intervertebral discs (IVDs) have been directly correlated to the development of these conditions 4,5 . Degeneration of the IVD is a progressive age-related disorder. Symptomatic relief may be achieved utilising current therapeutic strategies; however such strategies fail to address the underlying pathogenesis and aberrant cell biology and thus are ineffective for long-term treatment of this disease. The research community therefore continues to strive to improve understanding of the cellular and molecular biology of the healthy and degenerate disc in order to inform development of novel regenerative strategies.In order for effective regenerative strategies to be developed, it is essential that the phenotype of cells intended for recapitulation is fully elucidated. Cells of the adult human NP have routinely been likened to articular chondrocyte (AC) cells, with regards to both phenotype and morphology 6 . However, clear distinctions in the ECM produced by AC and NP cells have been demonstrated 7 , which has implications for the hydration state and

Galectins‐1 and ‐3 in Human Intervertebral Disc Degeneration: Non‐Uniform Distribution Profiles and Activation of Disease Markers Involving NF‐κB by Galectin‐1

“…Age-related changes of Gal-3 expression have already been documented in the developing human vertebral column 17 and in a comparison of NP cells between young (29-39 years) and mature (40-59 years) adults. 23 In contrast, Gal-1 expression-that significantly correlated with histopathological and MRI-based evidence for degeneration-did not correlate with patient age. This observation points to the possibility that Gal-1 may JOURNAL OF ORTHOPAEDIC RESEARCH ® OCTOBER 2019 qualify as functional disease marker, warranting efforts to design and test highly specific antagonists such as the recently reported Gal-3-like Gal-1 variant.…”

“…Concerning the studied galectins, Gal‐3 presence significantly correlated with age. Age‐related changes of Gal‐3 expression have already been documented in the developing human vertebral column and in a comparison of NP cells between young (29–39 years) and mature (40–59 years) adults . In contrast, Gal‐1 expression—that significantly correlated with histopathological and MRI‐based evidence for degeneration—did not correlate with patient age.…”

“…[15][16][17][18] Thus, Gal-3-alone or in combination with CD24 and carbonic anhydrase 12-has acquired the status of an NP cell marker. [19][20][21][22][23] Gal-1 presence was reported in human, porcine and rat IVDs in NP and anulus fibrosus (AF) cells, in which its distribution pattern was similar to that of the matrix glycoprotein laminin (isoform LM-511), 24,25 a known counterreceptor of Gal-1 and -3. 26,27 Functionally, Gal-3 presence has been assumed to affect NP cell survival 28 or "the destructive potential" of NP cells.…”

Latest advances in intervertebral disc development and progenitor cells

“…54 In most vertebrates, there is a progressive postnatal loss of large vacuolated notochord cells and the NP becomes instead populated by small chondrocyte-like cells. 55,56 In humans, cells of the NP change markedly with age; by skeletal maturity, despite maintaining expression of notochord markers (including brachyury, galectin-3, and CD24), 57 cells of the NP assume distinct phenotypic and molecular characteristics. [58][59][60][61][62] The loss of notochord cells from the NP is associated with the onset of degenerative changes in the IVD, suggesting that these cells are required for NP maintenance.…”

“…55,63,64 A number of recent studies have begun to characterize the NP cell molecular phenotype and changes associated with age and degeneration in humans. 57,65,66 The fate of the notochord cells within the NP has long been debated. It has been proposed that small chondrocyte-like NP cells were mesenchyme-derived, populating the NP following migration from the surrounding cartilage endplate (CEP) 67 or originating from transient amplifying cells in the perichondrium at the periphery of the disc.…”