title: N-Cadherin-Mediated Signaling Regulates Cell Phenotype for Nucleus Pulposus Cells of the Intervertebral Disc.
abstract: Juvenile nucleus pulposus (NP) cells of the intervertebral disc (IVD) are large, vacuolated cells that form cell clusters with strong cell-cell interactions. With maturation and aging, NP cells lose their ability to form these cell clusters, with aging-associated changes in NP cell phenotype, morphology, and proteoglycan synthesis that may contribute to IVD degeneration. Therefore, it is important to understand the mechanisms governing juvenile NP cell cluster behavior towards the goal of revealing factors that can promote juvenile, healthy NP cell phenotypes. N-cadherin has been identified as a cell-cell adhesion marker that is present in juvenile NP cells, but disappears with age. The goal of this study was to reveal the importance of N-cadherin in regulating cell-cell interactions in juvenile NP cell cluster formation and test for a regulatory role in maintaining a juvenile NP phenotypein vitro. Juvenile porcine IVD cells, of notochordal origin, were promoted to form cell clustersin vitro, and analyzed for preservation of the juvenile NP phenotype. Additionally, cadherin-blocking experiments were performed to prevent cluster formation in order to study the importance of cluster formation in NP cell signaling. Findings reveal N-cadherin-mediated cell-cell contacts promote cell clustering behavior and regulate NP cell matrix production and preservation of NP-specific markers. Inhibition of N-cadherin-mediated contacts resulted in loss of all features of the juvenile NP cell. These results establish a regulatory role for N-cadherin in juvenile NP cells, and suggest that preservation of the N-cadherin mediated cell-cell contact is important for preserving juvenile NP cell phenotype and morphology.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC 27713, USA.
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hwang
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC 27713, USA.
authors.forename: Liufang
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Orthopaedics, Emory Spine Center, Atlanta, GA 30329, USA.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Michael
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27713, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Richardson
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27713, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC 27713, USA ; Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27713, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Setton
keywords: Cell–cell interactions; Intervertebral disc; N-cadherin; Nucleus pulposus
references.citation: Bone Joint Res. 2013 Aug 19;2(8):169-78
references.pmid: 23958792
references.citation: J Orthop Res. 2001 Jul;19(4):597-604
references.pmid: 11518268
references.citation: Eur Cell Mater. 2011 Jun 20;21:523-32
references.pmid: 21710443
references.citation: Matrix Biol. 2001 Apr;20(2):107-21
references.pmid: 11334712
references.citation: PLoS One. 2011;6(11):e27170
references.pmid: 22087260
references.citation: Annu Rev Biomed Eng. 2006;8:259-87
references.pmid: 16834557
references.citation: Arthritis Rheum. 2010 Dec;62(12):3695-705
references.pmid: 20722018
references.citation: Semin Cancer Biol. 2005 Oct;15(5):378-86
references.pmid: 15975825
references.citation: Curr Opin Cell Biol. 2003 Oct;15(5):509-14
references.pmid: 14519384
references.citation: Spine (Phila Pa 1976). 2002 Dec 1;27(23):2631-44
references.pmid: 12461389
references.citation: Breast Cancer Res Treat. 1998 Sep;51(1):57-69
references.pmid: 9877029
references.citation: J Cell Sci. 2001 Feb;114(Pt 4):629-41
references.pmid: 11171368
references.citation: Spine (Phila Pa 1976). 2004 Dec 1;29(23):2691-9
references.pmid: 15564918
references.citation: J Cell Biol. 2003 Jan 6;160(1):11-6
references.pmid: 12507993
references.citation: J Cell Biol. 2002 Sep 2;158(5):953-65
references.pmid: 12213839
references.citation: Nat Rev Mol Cell Biol. 2010 Jul;11(7):502-14
references.pmid: 20571587
references.citation: Eur Spine J. 2008 Dec;17 Suppl 4:452-8
references.pmid: 19005704
references.citation: J Am Acad Orthop Surg. 2004 Mar-Apr;12(2):106-15
references.pmid: 15089084
references.citation: Connect Tissue Res. 2009;50(5):294-306
references.pmid: 19863388
references.citation: J Orthop Res. 2007 Jun;25(6):829-40
references.pmid: 17318895
references.citation: Spine (Phila Pa 1976). 1996 May 15;21(10):1174-84
references.pmid: 8727192
references.citation: Spine (Phila Pa 1976). 2011 Jan 15;36(2):153-9
references.pmid: 20671592
references.citation: J Anat. 2007 Oct;211(4):444-52
references.pmid: 17672847
references.citation: Annu Rev Cell Dev Biol. 2003;19:207-35
references.pmid: 14570569
references.citation: Eur Spine J. 2007 Nov;16(11):1892-8
references.pmid: 17661094
references.citation: Eur Spine J. 2006 Aug;15 Suppl 3:S303-11
references.pmid: 16547755
references.citation: Rheumatology (Oxford). 2014 Apr;53(4):600-10
references.pmid: 24049099
references.citation: Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a002915
references.pmid: 20182623
references.citation: J Orthop Res. 2012 Nov;30(11):1746-52
references.pmid: 22615104
references.citation: JAMA. 2013 Aug 14;310(6):591-608
references.pmid: 23842577
references.citation: J Clin Invest. 1996 Aug 15;98(4):996-1003
references.pmid: 8770872
references.citation: BMC Musculoskelet Disord. 2000 Oct 23;1:1
references.pmid: 11231882
references.citation: Arthritis Res Ther. 2003;5(3):120-30
references.pmid: 12723977
references.citation: Acta Biomater. 2014 Mar;10(3):1102-11
references.pmid: 24287160
references.citation: Genes Dev. 2006 Dec 1;20(23):3199-214
references.pmid: 17158740
references.citation: Blood. 2012 Feb 16;119(7):1623-33
references.pmid: 22174153
references.citation: Spine (Phila Pa 1976). 1995 Jun 1;20(11):1307-14
references.pmid: 7660243
references.citation: Spine (Phila Pa 1976). 2004 May 15;29(10):1099-104
references.pmid: 15131437
references.citation: Biomaterials. 2013 Oct;34(30):7381-8
references.pmid: 23849345
references.citation: J Cell Biol. 1994 Jun;125(6):1341-52
references.pmid: 8207062
references.citation: Cold Spring Harb Perspect Biol. 2009 Nov;1(5):a002949
references.pmid: 20066120
references.citation: Regen Med. 2013 Jan;8(1):75-87
references.pmid: 23259807
references.citation: J Biomech Eng. 2014 Feb;136(2):021010
references.pmid: 24390195
references.citation: J Anat. 2004 Nov;205(5):357-62
references.pmid: 15575884
references.citation: PLoS One. 2012;7(12):e52020
references.pmid: 23284858
references.citation: Arthritis Res Ther. 2010;12(1):R22
references.pmid: 20149220
references.citation: Cancer Inform. 2007 Feb 04;3:11-7
references.pmid: 19455231
references.citation: Dev Dyn. 2002 Oct;225(2):195-204
references.pmid: 12242719