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

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

Acknowledgments

This work was supported by Action Arthritis and by the Research Sustainability Fund (Norfolk and Norwich University Hospital).

Disclosure

The authors report no conflicts of interest in this work.