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The biomechanical role of the chondrocyte pericellular matrix in articular cartilag

Posted on:2005-06-09Degree:Ph.DType:Dissertation
University:Duke UniversityCandidate:Alexopoulos, Leonidas GFull Text:PDF
GTID:1454390008489928Subject:Biomedical engineering
Abstract/Summary:
Articular cartilage lines the surfaces of diarthrodial joints and serves as the low-friction, load-bearing material for joint motion. A single population of cells, termed chondrocytes, is responsible for maintaining the extracellular matrix (ECM) of this tissue. During normal joint activity, chondrocytes are exposed to a complex mechanical environment that in conjunction with other biochemical factors plays an important role in cartilage homeostasis and in the development of osteoarthritis.;Chondrocytes in articular cartilage are enclosed in a collagen type VI rich matrix known as the pericellular matrix (PCM), which together with the chondrocyte has been termed the "chondron". While the precise function of the PCM is not known there has been considerable speculation that it plays a major role in regulating the biomechanical environment of the chondrocyte.;The focus of this study was to quantify the biomechanical function of the PCM and determine the role of the presence of type VI collagen. To accomplish that, a novel chondron isolation technique was developed, mechanical tests on isolated chondrons were performed, and analytical and computational models were developed to determine the mechanical properties of the PCM. These properties were then incorporated into a biphasic finite element model and simulation tests of unconfined compression were performed. Our findings suggest that the PCM has an amplifying effect on the strain environment but significantly reduces the local stress and fluid flow environment of the chondrocyte. Osteoarthritic alterations on the mechanical properties of ECM and PCM have a significant impact on the cell's mechanical environment.;The role of type VI collagen in articular cartilage was investigated by using collagen type VI knockout mice. Histological, radiological, immunohistochemical, and mechanical test analyses were performed in normal and knockout mice. Our findings suggest that collagen VI plays a major role in the PCM stiffness. In addition, our findings provide direct evidence that collagen type VI might have a significant role on the osteochondral ossification process by modulating the chondrocyte and mesenchymal cell differentiation and proliferation activities. Furthermore, abnormal mechanical loads due to the lack of type VI collagen may result in decreased bone mineral density and development of osteoarthritis.
Keywords/Search Tags:Type VI, VI collagen, Mechanical, Role, Articular, Chondrocyte, PCM, Matrix
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