title: Long-term load duration induces N-cadherin down-regulation and loss of cell phenotype of nucleus pulposus cells in a disc bioreactor culture.
abstract: Long-term exposure to a mechanical load causes degenerative changes in the disc nucleus pulposus (NP) tissue. A previous study demonstrated that N-cadherin (N-CDH)-mediated signalling can preserve the NP cell phenotype. However, N-CDH expression and the resulting phenotype alteration in NP cells under mechanical compression remain unclear. The present study investigated the effects of the compressive duration on N-CDH expression and on the phenotype of NP cells in anex vivodisc organ culture. Porcine discs were organ cultured in a self-developed mechanically active bioreactor for 7 days. The discs were subjected to different dynamic compression durations (1 and 8 h at a magnitude of 0.4 MPa and frequency of 1.0 Hz) once per day. Discs that were not compressed were used as controls. The results showed that long-term compression duration (8 h) significantly down-regulated the expression of N-CDH and NP-specific molecule markers (Brachyury, Laminin, Glypican-3 and Keratin 19), attenuated Alcian Blue staining intensity, decreased glycosaminoglycan (GAG) and hydroxyproline (HYP) contents and decreased matrix macromolecule (aggrecan and collagen II) expression compared with the short-term compression duration (1 h). Taken together, these findings demonstrate that long-term load duration can induce N-CDH down-regulation, loss of normal cell phenotype and result in attenuation of NP-related matrix synthesis in NP cells.
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
authors.forename: Ruijie
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Department of Orthopedic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chengmin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ouyang
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Tu
authors.affiliation: Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China zq_tlh@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D019149:Bioreactors; D015820:Cadherins / Q000032:analysis / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation; D004867:Equipment Design; D000070614:Nucleus Pulposus / Q000166:cytology* / Q000378:metabolism; D009924:Organ Culture Techniques / Q000295:instrumentation; D010641:Phenotype; D013314:Stress, Mechanical; D013552:Swine; D016474:Weight-Bearing
chemical_list: D015820:Cadherins
keywords: N-cadherin; compression; degeneration; nucleus pulposus; organ culture