title: The role of angiopoietin-2 in nucleus pulposus cells during human intervertebral disc degeneration.
abstract: Although evidence shows that intervertebral disc degeneration is generally characterized by angiogenesis, the role of angiopoietin has not been investigated. This study examined the presence of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) within the native intervertebral disc (IVD) and elucidated their functions in the regulation of nucleus pulposus (NP) cells. Initial investigation of uncultured NP tissue revealed that Ang-1 and Ang-2 were expressed by native NP cells. Ang-2 expression was significantly increased in infiltrated and degenerate samples relative to normal samples. The ratio of Ang-2/Ang-1 in tissues from patients increased markedly with increasing age and level of degeneration of the IVD. The ratio of both Ang-2/Ang-1 mRNA and protein increased over time when cells were subjected to constant pressure at 1 Mpa in vitro. Our findings indicate that Ang-2 plays a role in suppressing cell adhesion and viability, and promotes the apoptosis of NP cells and that Ang-2 can inhibit the pathways stimulated by Ang-1 and fibronectin. Ang-2 release during IVD degeneration causes higher ratio of Ang-2 to Ang-1, further inhibits NP cell viability and adhesion, promoting apoptosis by blocking PI3K/Akt signaling. The present study therefore provides new insights into the role of the angiopoietin-Tie system in the pathogenesis of IVD degeneration.
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, First Hospital of Wuhan, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xinghuo
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Tu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yingle
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Cao
authors.initials: C
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D042683:Angiopoietin-1 / Q000032:analysis / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000032:analysis / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D008875:Middle Aged; D000070614:Nucleus Pulposus / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2