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N-cadherin is Key to Expression of the Nucleus Pulposus Cell Phenotype under Selective Substrate Culture Conditions.

Publication ,  Journal Article
Hwang, PY; Jing, L; Chen, J; Lim, F-L; Tang, R; Choi, H; Cheung, KM; Risbud, MV; Gersbach, CA; Guilak, F; Leung, VY; Setton, LA
Published in: Scientific reports
June 2016

Nucleus pulposus (NP) cells of the intervertebral disc are essential for synthesizing extracellular matrix that contributes to disc health and mechanical function. NP cells have a unique morphology and molecular expression pattern derived from their notochordal origin, and reside in N-cadherin (CDH2) positive cell clusters in vivo. With disc degeneration, NP cells undergo morphologic and phenotypic changes including loss of CDH2 expression and ability to form cell clusters. Here, we investigate the role of CDH2 positive cell clusters in preserving healthy, biosynthetically active NP cells. Using a laminin-functionalized hydrogel system designed to mimic features of the native NP microenvironment, we demonstrate NP cell phenotype and morphology is preserved only when NP cells form CDH2 positive cell clusters. Knockdown (CRISPRi) or blocking CDH2 expression in vitro and in vivo results in loss of a healthy NP cell. Findings also reveal that degenerate human NP cells that are CDH2 negative can be promoted to re-express CDH2 and healthy, juvenile NP matrix synthesis patterns by promoting cell clustering for controlled microenvironment conditions. This work also identifies CDH2 interactions with β-catenin-regulated signaling as one mechanism by which CDH2-mediated cell interactions can control NP cell phenotype and biosynthesis towards maintenance of healthy intervertebral disc tissues.

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Published In

Scientific reports

DOI

EISSN

2045-2322

ISSN

2045-2322

Publication Date

June 2016

Volume

6

Start / End Page

28038

Related Subject Headings

  • beta Catenin
  • Young Adult
  • Swine
  • Signal Transduction
  • Phenotype
  • Nucleus Pulposus
  • Middle Aged
  • Humans
  • Gene Knockdown Techniques
  • Child
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hwang, P. Y., Jing, L., Chen, J., Lim, F.-L., Tang, R., Choi, H., … Setton, L. A. (2016). N-cadherin is Key to Expression of the Nucleus Pulposus Cell Phenotype under Selective Substrate Culture Conditions. Scientific Reports, 6, 28038. https://doi.org/10.1038/srep28038
Hwang, Priscilla Y., Liufang Jing, Jun Chen, Foon-Lian Lim, Ruhang Tang, Hyowon Choi, Kenneth M. Cheung, et al. “N-cadherin is Key to Expression of the Nucleus Pulposus Cell Phenotype under Selective Substrate Culture Conditions.Scientific Reports 6 (June 2016): 28038. https://doi.org/10.1038/srep28038.
Hwang PY, Jing L, Chen J, Lim F-L, Tang R, Choi H, et al. N-cadherin is Key to Expression of the Nucleus Pulposus Cell Phenotype under Selective Substrate Culture Conditions. Scientific reports. 2016 Jun;6:28038.
Hwang, Priscilla Y., et al. “N-cadherin is Key to Expression of the Nucleus Pulposus Cell Phenotype under Selective Substrate Culture Conditions.Scientific Reports, vol. 6, June 2016, p. 28038. Epmc, doi:10.1038/srep28038.
Hwang PY, Jing L, Chen J, Lim F-L, Tang R, Choi H, Cheung KM, Risbud MV, Gersbach CA, Guilak F, Leung VY, Setton LA. N-cadherin is Key to Expression of the Nucleus Pulposus Cell Phenotype under Selective Substrate Culture Conditions. Scientific reports. 2016 Jun;6:28038.

Published In

Scientific reports

DOI

EISSN

2045-2322

ISSN

2045-2322

Publication Date

June 2016

Volume

6

Start / End Page

28038

Related Subject Headings

  • beta Catenin
  • Young Adult
  • Swine
  • Signal Transduction
  • Phenotype
  • Nucleus Pulposus
  • Middle Aged
  • Humans
  • Gene Knockdown Techniques
  • Child