Proteomic analysis of synovial fluid and cartilage from both knee and shoulder is providing a detailed view of how arthritic joints differ from healthy joints. Inflammatory cytokines are upregulated (no surprise), but so are signals involved in wound healing: fibrinogen, aggregan core protein, and messengers in the alternate complement pathway. These results validate an old theory of osteoarthritis (OA) as a state of chronic wound healing, with implications for early diagnosis and treatment.
Hear Reuben Gobezie MD, who has been involved in many of these interdisciplinary studies, describe this recent line of research and what it means for the future of osteoarthritis management. Dr. Gobezie has spent much of his career in molecular research. In August 2012, he became director of the Cleveland Shoulder Institute at University Hospitals of Cleveland.
• Can you describe the research briefly?
• At the meeting you mentioned inflammatory cytokines, but reports have implicated fibrinogen, aggrecan, and complement. What are the implications of that? How do they work together?
• What are the implications for treatment or our understanding of the condition?
• Would you say that the implications of this research are greater in the field of finding biomarkers for early OA or in finding treatments to slow the process?
• Would you say that the research validates or provides insights into phenomena that we have found puzzling about osteoarthritis, until now?
|From the AAOS Meeting: Osteoarthritis as a Chronic Wound|
From the AAOS Meeting: Osteoarthritis as a Chronic Wound
"The complement system [is] very much overexpressed and ever-present in arthritis ... The alternate pathway of complement was key in disease progression. We don't really know why."
"I think this data would support the theory that early meniscal tears from mechanical trauma, which is not arthritis, and your body's inability to heal the avascular areas of the meniscus, that in of itself starts a chronic inflammatory cascade ... "
"It's not just this idea that Grandma got old and just "wore it out", or that it's purely the cartilage as the source of the problem as an isolated entity. Rather it's ... a biological impetus and a mechanical problem. This chronic wound concept really does tie that together."
For further reference:
Wanner JP, Subbaiah RS, Shishani Y et al. Proteomic Analysis of Shoulder Osteoarthritis. Presentation abstract, 2013 American Academy of Orthopaedic Surgeons Annual Meeting.
Ritter SY, Subbaiah R, Bebek G et al. Proteomic analysis of synovial fluid from the osteoarthritic knee: Comparison with transcriptome analyses of joint tissue. Arthritis Rheum (2013) Feb 11. doi: 10.1002/art.37823. [Epub ahead of print]
Wang Q, Rozelle AL, Lepus CM et al. Identification of a central role for complement in osteoarthritis. Nat Med (2011) 17:1674-1679