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iDEA: DREXEL LIBRARIES E-REPOSITORY AND ARCHIVES

iDEA: DREXEL LIBRARIES E-REPOSITORY AND ARCHIVES

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Novel Biomechanical and Biochemical Signatures of Post-Traumatic Osteoarthritis

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Title
Novel Biomechanical and Biochemical Signatures of Post-Traumatic Osteoarthritis: A Murine Model Study
Author(s)
Roberts, Ian Lodge
Advisor(s)
Han, Lin
Keywords
Biomedical engineering; Cartilage--Diseases; Osteoarthritis; Immunohistochemistry
Date
2016-06
Publisher
Drexel University
Thesis
M.S., Biomedical Engineering -- Drexel University, 2016
Abstract
Post-traumatic osteoarthritis (PTOA) is an inflammatory-based cartilage degenerating disease that develops after joint injury. It results in the breakdown of articular cartilage in the joints, leading to pain and loss of mobility over time, eventually requiring surgical intervention. Approximately 50% of patients who suffer a serious joint injury such as an anterior cruciate ligament (ACL) tear will develop diagnosable PTOA within 10-15 years. In the United States, more than 5 million people have various degrees of PTOA in the hip, ankle, or knee. Despite its prevalence, there are few treatments for cartilage injury, with most medical intervention centered around palliative care once PTOA has been diagnosed. Pharmacological solutions are limited, due to the complexity and difficulty of studying chondrocyte behavior and the cartilage matrix structure-function relationship in vivo. In this study, cartilage injury was induced in a murine model by the destabilization of the medial meniscus (DMM) surgery on the right knee joint. After the procedure, chondrocyte signaling behavior was studied by examining the expression of bone morphogenetic protein-2 (BMP2) and its associated intracellular downstream mediator, pSmad1/5/8, using immunohistochemistry. These two proteins are important homeostatic cytokines in cartilage, instructing chondrocytes to synthesize new extra-cellular matrix (ECM), mainly type II collagen and aggrecan. Changes in the matrix structure of cartilage were examined via changes in aggrecan and decorin. Aggrecan is a large, highly charged protein that binds to water, reducing its flow, and giving cartilage its innate force-cushioning properties. Decorin is an important, small leucine-rich proteoglycan, which regulates the formation and homeostasis of cartilage ECM through binding to other proteoglycans, such as aggrecan. In addition, changes in function-relevant mechanical properties were also examined by atomic force microscopy (AFM)-based Nanoindentation on condyle cartilage surfaces. After the DMM surgery, cartilage homeostasis was disrupted. BMP2 and pSmad1/5/8 staining increased, suggesting anabolic and catabolic changes to chondrocyte function. Aggrecan concentration was reduced, signifying degradation of the ECM. Meanwhile, the active involvement of decorin in the ECM degradation process is indicated by the substantial reduction of aggrecan in decorin-null mice. Furthermore, cartilage after DMM showed significantly lower nanoindentation modulus than the control after Sham surgery, highlighting OA-induced loss of joint function. These biochemical and biomechanical results prove insights into the concomitant biological and biomechanical changes of cartilage during the progression of injury-induced PTOA.
URI
http://hdl.handle.net/1860/idea:6840
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