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Chondrocyte responses to neurovascular peptides, cytokines, and a 3D environment: focus on ADAMs

Authors Bevan D, Baker N, Goldring M, Donell S, Gavrilovic J

Received 8 March 2016

Accepted for publication 11 May 2016

Published 1 September 2016 Volume 2016:3 Pages 63—74

DOI https://doi.org/10.2147/MNM.S108003

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Yoshifumi Itoh


Damon Bevan,1 Natasha Baker,1 Mary B Goldring,2 Simon T Donell,3 Jelena Gavrilovic1

1School of Biological Sciences, University of East Anglia, Norwich, UK; 2Hospital for Special Surgery, Research Division, Weill Cornell Medical College, New York, NY, USA; 3Department of Orthopaedics, Norfolk and Norwich University Hospital, Norwich, UK

Abstract: Chondrocyte exposure to inflammatory stimuli in several arthritic conditions, including osteoarthritis, results in the well-characterized induction of extracellular matrix degrading proteinases, notably members of a disintegrin and metalloproteinase (ADAM) with thrombospondin domains and matrix metalloproteinase families. Here we briefly review the less-studied ADAM family of proteinases in chondrocyte and cartilage biology. Following damage, cartilage is exposed to neurovascular peptides, and in this study we hypothesized that substance P and bradykinin, alongside inflammatory cytokines, may modulate chondrocyte steady-state messenger RNA levels for the proteolytic ADAM family members as well as for key cytokines and neuropeptides. We compared chondrocytes cultured in both two-dimensional and three-dimensional (3D) environments and found that 3D culture generally resulted in repression of expression of the genes under investigation, with the exception of anti-inflammatory interleukin 10 which was markedly upregulated in a 3D environment. Substance P and bradykinin had little effect on ADAM family expression, but further investigation revealed that a combination of bradykinin and cytokines led to enhanced expression of ADAM28 and a synergistic upregulation of interleukin 6, also observed under hypoxic conditions. Overall these data reveal wider chondrocyte responses to neurovascular peptides which may have an impact in an osteoarthritis context.

Keywords: chondrocyte, ADAM, metalloproteinase, cytokine; bradykinin

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