Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation

Feng Wang, Zeng-Xin Gao, Feng Cai, Arjun Sinkemani, Zhi-Yang Xie, Rui Shi, Ji-Nan Wei and Xiao-Tao Wu _

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Oncotarget. 2017; 8:57800-57812. https://doi.org/10.18632/oncotarget.18101

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Feng Wang1,2,*, Zeng-Xin Gao1,2,*, Feng Cai3,*, Arjun Sinkemani1,2, Zhi-Yang Xie1,2, Rui Shi1,2, Ji-Nan Wei2,4 and Xiao-Tao Wu1,2

1Department of Spine Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China

2Surgery Research Center, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China

3Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Soochow, Jiangsu Province, China

4Department of Orthopedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China

*These authors have contributed equally to this work

Correspondence to:

Xiao-Tao Wu, email: [email protected]

Keywords: intervertebral disc, notochord, notochord vacuolation, cytoplasmic vacuole, nucleus pulposus

Received: July 28, 2016     Accepted: May 01, 2017     Published: May 23, 2017


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, well-structured 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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