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Article: CK8 phosphorylation induced by compressive loads underlies the downregulation of CK8 in human disc degeneration by activating protein kinase C

TitleCK8 phosphorylation induced by compressive loads underlies the downregulation of CK8 in human disc degeneration by activating protein kinase C
Authors
Keywordscompressive load
cytokeratin 8
intervertebral disc degeneration
phosphorylation
protein kinase C
Issue Date2013
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/labinvest/
Citation
Laboratory Investigation, 2013, v. 93 n. 12, p. 1323-1330 How to Cite?
AbstractCytokeratin 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.
Persistent Identifierhttp://hdl.handle.net/10722/203245
ISSN
2023 Impact Factor: 5.1
2023 SCImago Journal Rankings: 1.243
ISI Accession Number ID
Grants

 

DC FieldValueLanguage
dc.contributor.authorSun, Z-
dc.contributor.authorGuo, YS-
dc.contributor.authorYan, SJ-
dc.contributor.authorWan, ZY-
dc.contributor.authorGao, B-
dc.contributor.authorWang, L-
dc.contributor.authorLiu, ZH-
dc.contributor.authorGao, Y-
dc.contributor.authorSamartzis, D-
dc.contributor.authorLan, LF-
dc.contributor.authorWang, HQ-
dc.contributor.authorLuo, ZJ-
dc.date.accessioned2014-09-19T13:11:30Z-
dc.date.available2014-09-19T13:11:30Z-
dc.date.issued2013-
dc.identifier.citationLaboratory Investigation, 2013, v. 93 n. 12, p. 1323-1330-
dc.identifier.issn0023-6837-
dc.identifier.urihttp://hdl.handle.net/10722/203245-
dc.description.abstractCytokeratin 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.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/labinvest/-
dc.relation.ispartofLaboratory Investigation-
dc.subjectcompressive load-
dc.subjectcytokeratin 8-
dc.subjectintervertebral disc degeneration-
dc.subjectphosphorylation-
dc.subjectprotein kinase C-
dc.titleCK8 phosphorylation induced by compressive loads underlies the downregulation of CK8 in human disc degeneration by activating protein kinase C-
dc.typeArticle-
dc.identifier.emailSamartzis, D: dspine@hku.hk-
dc.identifier.authoritySamartzis, D=rp01430-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/labinvest.2013.122-
dc.identifier.pmid24166186-
dc.identifier.scopuseid_2-s2.0-84888387584-
dc.identifier.hkuros238000-
dc.identifier.volume93-
dc.identifier.issue12-
dc.identifier.spage1323-
dc.identifier.epage1330-
dc.identifier.isiWOS:000327795600007-
dc.publisher.placeUnited Kingdom-
dc.relation.projectDevelopmental genomics and skeletal research-
dc.identifier.issnl0023-6837-

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