Inflammatory molecules produced by meniscus and synovium in early and end-stage osteoarthritis: a coculture study

Marta Favero, Elisa Belluzzi, Giovanni Trisolino, Mary B Goldring, Steven R Goldring, Augusto Cigolotti, Assunta Pozzuoli, Pietro Ruggieri, Roberta Ramonda, Brunella Grigolo, Leonardo Punzi, Eleonora Olivotto

Research output: Contribution to journalArticle

Abstract

The aim of this study was to identify the molecules and pathways involved in the cross-talk between meniscus and synovium that may play a critical role in osteoarthritis (OA) pathophysiology. Samples of synovium and meniscus were collected from patients with early and end-stage OA and cultured alone or cocultured. Cytokines, chemokines, metalloproteases, and their inhibitors were evaluated at the gene and protein levels. The extracellular matrix (ECM) changes were also investigated. In early OA cultures, higher levels of interleukin-6 (IL-6) and IL-8 messenger RNA were expressed by synovium and meniscus in coculture compared with meniscus cultured alone. RANTES release was significantly increased when the two tissues were cocultured compared with meniscus cultured alone. Increased levels of matrix metalloproteinase-3 (MMP-3) and MMP-10 proteins, as well as increased release of glycosaminoglycans and aggrecan CS846 epitope, were observed when synovium was cocultured with meniscus. In end-stage OA cultures, increased levels of IL-8 and monocyte chemoattractant protein-1 (MCP-1) proteins were released in cocultures compared with cultures of meniscus alone. Chemokine (C-C motif) ligand 21 (CCL21) protein release was higher in meniscus cultured alone and in coculture compared with synovium cultured alone. Increased levels of MMP-3 and 10 proteins were observed when tissues were cocultured compared with meniscus cultured alone. Aggrecan CS846 epitope release was increased in cocultures compared with cultures of either tissue cultured alone. Our study showed the production of inflammatory molecules by synovium and meniscus which could trigger inflammatory signals in early OA patients, and induce ECM loss in the progressive and final stages of OA pathology.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of Cellular Physiology
DOIs
Publication statusE-pub ahead of print - Nov 19 2018

Keywords

  • coculture
  • inflammation
  • knee
  • meniscus
  • osteoarthritis
  • synovium

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