title: CK8 phosphorylation induced by compressive loads underlies the downregulation of CK8 in human disc degeneration by activating protein kinase C.
abstract: Cytokeratin 8 (CK8) is a member of the cytokeratins family with multiple functions on the basis of its unique structural hallmark. The aberrant expression of CK8 and its phosphorylation are pertinent with various diseases. We have previously shown that CK8 exists in normal human nucleus pulposus (NP) cells and decreases as the intervertebral disc degenerates. However, the underlying molecular regulatory machinery of CK8 in intervertebral disc degeneration (IDD) has not been clarified. Here, we collected NP samples from patients with idiopathic scoliosis as control and IDD as degenerate groups. We found that CK8 expression decreased in IDD with an increased phosphorylation in degenerate NP cells. Moreover, NP cells were cultured under different compressive load schemes for diverse time duration. We found that compressive loads resulted in phosphorylation and disassembly of CK8 in a time-dependent and degree-dependent manner in vitro. The activation of protein kinase C was a significant molecular factor contributing to this phenomenon. Taken together, this study is the first to address the molecular mechanisms of CK8 downregulation in NP cells. Importantly, our findings provide clues regarding a molecular link between compressive loads and CK8 alterations, which shed a novel light on the etiology of IDD.
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Sun
authors.forename: Yun-Shan
authors.initials: YS
authors.lastname: Guo
authors.forename: Shi-Ju
authors.initials: SJ
authors.lastname: Yan
authors.forename: Zhong-Yuan
authors.initials: ZY
authors.lastname: Wan
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.forename: Zhi-Heng
authors.initials: ZH
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Dino
authors.initials: D
authors.lastname: Samartzis
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Lan
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Wang
authors.forename: Zhuo-Jing
authors.initials: ZJ
authors.lastname: Luo
mesh_terms: D000293:Adolescent; D000328:Adult; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000201:enzymology*; D053533:Keratin-8 / Q000378:metabolism*; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D013131:Spine / Q000502:physiology; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000502:physiology; D016474:Weight-Bearing; D055815:Young Adult
chemical_list: D053533:Keratin-8; C497255:PRKCE protein, human; D051744:Protein Kinase C-epsilon