Degradation of cartilage and meniscus tissues : an in vitro investigation in osteoarthritis development

Placeholder Show Content

Abstract/Contents

Abstract
Osteoarthritis is a debilitating disease that affects 27 million Americans. Major risk factors for osteoarthritis include mechanical injury and obesity. Prolonged exposure to mechanical overload in the knee joint, either by injury, malalignment, or obesity, is associated with early onset of osteoarthritis. Recent evidence demonstrates that adipose tissue is a metabolically active and produces systemic biofactors known as adipokines associated with numerous diseases including cardiovascular disease, hypertension, insulin resistance, rheumatoid arthritis, and osteoarthritis. Interestingly, obesity is a significant risk factor for hand osteoarthritis, suggesting a biologic link between obesity and osteoarthritis that is perhaps mediated through adipokines. While many studies investigating in vitro osteoarthritic degradation have focused on cartilage tissue, the menisci has received relatively little attention despite it's important functional role in joint stability and load transfer in the knee. The purpose of this thesis was to explore the relative susceptibility of cartilage and meniscal tissue degradation to in vitro mechanical overload and adipokine exposure using an immature bovine tissue explant model. To explore the injury response, explants of cartilage and meniscal tissues were compressed at various strain rates to create a spectrum of peak injury forces and cultured for up to nine days post-injury. To investigate whether adipose tissue and adipokines can biochemically induce changes in cartilage and meniscal tissues, explants of cartilage and meniscal tissue were incubated with infrapatellar fat pad or individual adipokines and assessed for altered matrix metabolism. Overall, results indicate that, while mechanically robust, meniscal tissue is vulnerable to biologic damage induced by mechanical overload and adipokines. We also demonstrate for the first time that meniscal tissue is more catabolically sensitive to adipokines than cartilage tissue. These results provide evidence that obesity-driven degradation of knee joint could be biochemically mediated and suggest meniscal degradation as a possible early event in osteoarthritis development.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2013
Issuance monographic
Language English

Creators/Contributors

Associated with Nishimuta, James Francis
Associated with Stanford University, Department of Mechanical Engineering.
Primary advisor Levenston, Marc Elliot
Thesis advisor Levenston, Marc Elliot
Thesis advisor Andriacchi, Th. P. (Thomas P.)
Thesis advisor Goodman, Stuart
Thesis advisor Smith, R. Lane (Robert Lane)
Advisor Andriacchi, Th. P. (Thomas P.)
Advisor Goodman, Stuart
Advisor Smith, R. Lane (Robert Lane)

Subjects

Genre Theses

Bibliographic information

Statement of responsibility James Francis Nishimuta.
Note Submitted to the Department of Mechanical Engineering.
Thesis Thesis (Ph.D.)--Stanford University, 2013.
Location electronic resource

Access conditions

Copyright
© 2013 by James Francis Nishimuta
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

Also listed in

Loading usage metrics...