Mechanical injury and inflammatory cytokines affect cartilage integrity and tissue homeostasis : a mass spectrometric analysis of proteins with relevance to arthritis

Osteoarthritis is characterized by synovial joint degeneration, and its cardinal pathological feature is degeneration and loss of the articular cartilage joint surface. While the aetiology of osteoarthritis is unknown, risk factors include gender, age, obesity, and prior joint injury. Joint injuries, including tears of the anterior cruciate ligament (ACL) and meniscus, increase the risk for the development of OA and involve both mechanical damage to cartilage, meniscus and synovial tissues, and tissue degradation associated with cytokine-induced inflammation. While the role of inflammatory cytokines in OA is still controversial, their role in rheumatoid arthritis is evidenced by the successful use of anti-TNF-ca and anti-IL-1 therapies to abrogate disease symptoms and progression. In vitro, both IL-13 and TNF-ca promote chondrocyte-mediated matrix degradation and inhibit cartilage matrix synthesis, while mechanical damage causes cell death, matrix damage, and decreased cell biosynthesis. Understanding the similarities and differences in cartilage responses to inflammatory cytokines and mechanical injury is important in understanding the catabolic-anabolic shifts that typify OA progression. Therefore, the objectives of this thesis were (1) to identify the role of TNF-a and IL-1 induced nitric oxide (NO) as a mediator of cartilage tissue damage;

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Stevens, Anna L. (Anna Lea)

Advisor dc:contributor.advisor

• Alan J. Grodzinsky and Steven R. Tannenbaum.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/37956

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/37956