Journal
ONCOTARGET
Volume 8, Issue 34, Pages 57800-57812Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.18101
Keywords
intervertebral disc; notochord; notochord vacuolation; cytoplasmic vacuole; nucleus pulposus
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Funding
- National Natural Science Foundation of China [81201423, 81272035, 81572170]
- Nanjing Health Bureau [YKK15249]
- Science and Technology Bureau of Jiangsu province [BL2013031]
- Project of Six Peak Talent of Jiangsu Province [WSW003]
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Notochord nucleus pulposus cells are characteristic of containing abundant and giant cytoplasmic vacuoles. This review explores the embryonic formation, biological function, and postnatal exhaustion of notochord vacuoles, aiming to characterize the signal network transforming the vacuolated nucleus pulposus cells into the vacuole-less chondrocytic cells. Embryonically, the cytoplasmic vacuoles within vertebrate notochord originate from an evolutionarily conserved vacuolation process during neurulation, which may continue to provide mechanical and signal support in constructing a mammalian intervertebral disc. For full vacuolation, a vacuolating specification from dorsal organizer cells, synchronized convergent extension, wellstructured notochord sheath, and sufficient post-Golgi trafficking in notochord cells are required. Postnatally, age-related and species-specific exhaustion of vacuolated nucleus pulposus cells could be potentiated by Fas- and Fas ligand-induced apoptosis, intolerance to mechanical stress and nutrient deficiency, vacuole-mediated proliferation check, and gradual de-vacuolation within the avascular and compression loaded intervertebral disc. These results suggest that the notochord vacuoles are active and versatile organelles for both embryonic notochord and postnatal nucleus pulposus, and may provide novel information on intervertebral disc degeneration to guide cell-based regeneration.
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