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

2017; Impact Journals LLC; Volume: 8; Issue: 34 Linguagem: Inglês

10.18632/oncotarget.18101

1949-2553

Feng Wang, Zengxin Gao, Feng Cai, Arjun Sinkemani, Zhi‐Yang Xie, Rui Shi, Ji-Nan Wei, Xiaotao Wu,

Spine and Intervertebral Disc Pathology

// Feng Wang 1, 2, * , Zeng-Xin Gao 1, 2, * , Feng Cai 3, * , Arjun Sinkemani 1, 2 , Zhi-Yang Xie 1, 2 , Rui Shi 1, 2 , Ji-Nan Wei 2, 4 and Xiao-Tao Wu 1, 2 1 Department of Spine Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China 2 Surgery Research Center, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China 3 Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Soochow, Jiangsu Province, China 4 Department 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: wuxiaotaospine@163.com Keywords: intervertebral disc, notochord, notochord vacuolation, cytoplasmic vacuole, nucleus pulposus Received: July 28, 2016 Accepted: May 01, 2017 Published: May 23, 2017 ABSTRACT 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.