Damage-associated molecular patterns in the pathogenesis of osteoarthritis: potentially novel therapeutic targets

John H. Rosenberg, Vikrant Rai, Matthew Dilisio, Devendra K. Agrawal

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Osteoarthritis (OA) is a chronic disease that degrades the joints and is often associated with increasing age and obesity. The two most common sites of OA in adults are the knee and hip joints. Increased mechanical stress on the joint from obesity can cause the articular cartilage to degrade and release damage-associated molecular patterns (DAMPs). These DAMPs are involved in various molecular pathways that interact with nuclear factor-kappa B and result in the transcription of inflammatory cytokines and activation of matrix metalloproteinases that progressively destroy cartilage. This review focuses on the interactions and contribution to the pathogenesis and progression of OA through the DAMPs: high-mobility group box 1 (HMGB-1), the receptor for advanced glycation end-products (RAGE), the alarmin proteins S100A8 and S100A9, and heparan sulfate. HMGB-1 is released from damaged or necrotic cells and interacts with toll-like receptors (TLRs) and RAGE to induce inflammatory signals, as well as behave as an inflammatory cytokine to activate innate immune cells. RAGE interacts with HMGB-1, advanced glycation end-products, and innate immune cells to increase local inflammation. The alarmin proteins are released following cell damage and interact through TLRs to increase local inflammation and cartilage degradation. Heparan sulfate has been shown to facilitate the binding of HMGB-1 to RAGE and could play a role in the progression of OA. Targeting these DAMPs may be the potential therapeutic strategies for the treatment of OA.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMolecular and Cellular Biochemistry
DOIs
StateAccepted/In press - May 4 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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