by Lee Kwong Man, Simon. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 239-277). / ABSTRACT --- p.i / ACKNOWLEDGMENT --- p.vi / PUBLICATIONS --- p.vii / ABBREVIATIONS --- p.viii / TABLE OF CONTENT --- p.xi / Chapter CHAPTER ONE --- General Introduction --- p.1 / Chapter CHAPTER TWO --- Identification and Biochemical Characterization of Various Differentiative Growth Plate Chondrocytes by Countercurrent Centrifugal Elutriation --- p.8 / Chapter CHAPTER THREE --- Differential Expression of Glycoconjugates during Endochondral Ossification in Porcine Growth Plate --- p.50 / Chapter CHAPTER FOUR --- Intra- & Extra-Cellular Free Calcium Activities of Porcine Growth Plate Chondrocytes at Various Stages of Maturation --- p.90 / Chapter CHAPTER FIVE --- A New In Situ Model for Electrophysiological Characterization of Ionic Channels in Growth Plate Chondrocytes --- p.144 / Chapter CHAPTER SIX --- Effects of Quinolones on Growth Plate Chondrocytes --- p.201 / Chapter CHAPTER SEVEN --- Summary and Conclusion --- p.226 / BIBLIOGRAPHY --- p.239

The primary cilium is a microtubule-based organelle present on the majority of interphase cells where it functions as a hub for numerous signalling pathways including hedgehog signalling. Chondrocytes, the unique cellular component of articular cartilage, possess primary cilia which are required for mechanotransduction and maintenance of a healthy extracellular matrix. However in osteoarthritis there is an increase in primary cilia length and prevalence associated with aberrant activation of hedgehog signalling which promotes cartilage degradation. The aim of this thesis was therefore to examine the influence of biophysical stimuli on chondrocyte primary cilia structure and function, relating changes in ciliary length to perturbations in hedgehog signalling. An in vitro mechanical loading model was established to study the influence of cyclic tensile strain on chondrocyte primary cilia. Loading at 10% strain activated hedgehog signalling measured by expression of Gli1 and Ptch1. Cilia progressively disassembled in response to increasing levels of mechanical strain in a manner dependent upon tubulin deacetylation. Cilia disassembly at 20% strain was associated with the loss of mechanosensitive hedgehog signalling despite continued expression of hedgehog ligand (Ihh). Therefore this behaviour may function as a protective mechanism limiting hedgehog-mediated cartilage degradation in response to high levels of mechanical strain. To further understand the influence the extracellular environment exerts over ciliary function, a second in vitro model was developed investigating the effects of thermal stress. In chondrocytes and fibroblasts, primary cilia underwent rapid resorption in response to elevated temperature and ligand mediated hedgehog signalling was inhibited. These studies demonstrate that regulated disassembly of the cilium in response to physical stress modulates both cilia size and function. In particular, the findings suggest that changes in the chondrocyte physical environment affect cilia structure and function and may therefore be an important factor in the aetiology of cartilage disease.

Thesis (Ph. D.)--Ohio State University, 2006. / Full text release at OhioLINK's ETD Center delayed at author's request

Thesis (Ph. D.)--University of Rhode Island, 2005. / Typescript. Includes bibliographical references (leaves 189-201).

Acetabular labral tears are associated with hip osteoarthritis. A current surgical treatment strategy for a torn labrum, labral resection, has recently shown poor patient outcomes with radiographic signs of osteoarthritis two-years post-operation. Since mechanical factors play a role in the etiology of osteoarthritis, identifying the mechanical role of the labrum may enhance current surgical treatment strategies. In this pilot study, we assessed the relationship between mean cartilage strain, maximum cartilage strain and the three-dimensional cartilage strain distribution in six human cadaver hips with various pathologic conditions of the labrum. We developed a novel technique of mapping cartilage strain using quantitative magnetic resonance imaging (qMRl). qMRl provides a non-invasive means of quantifying the cartilage strain distribution in the hip in three dimensions. Each specimen was assessed first with an intact labrum, then after surgically simulating a longitudinal peripheral labral tear, then after arthroscopically repairing the tear, and after labral resection. We validated the precision of the technique through use of an additional specimen which served as a control. To minimize motion artifact in the high-resolution MR images, we determined that 225 minutes was required for cartilage to reach a steady-state thickness under load. We also determined 16.5 hours was required for cartilage to recover to a steady-state unloaded thickness. The difference in mean and maximum cartilage strain when the labrum was repaired and resected was assessed using a paired t-test. We found that the resected group had an increased mean and maximum cartilage strain of 4% and 6%, respectively and the 3D cartilage strain distribution was elevated throughout the region of interest. When the condition of the intact labrum was compared to the torn labrum, we found no change in mean and maximum cartilage strain, and little obvious change in the 3D pattern of cartilage strain distribution. Based on our findings of increased cartilage strain after labral resection when compared to labral repair, we hypothesize that the labrum’s contribution of additional surface area assists in load distribution, which spares cartilage from excessive loads. We therefore recommend that the longitudinal peripheral torn labrum should not be resected if it is possible to be repaired, because in vivo, labral resection may create an environment with increased articular cartilage strain, which is thought to be associated with cartilage degeneration.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 339-368). Also available online.

Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: tissue engineering; biosynthesis; chondrocyte. Includes bibliographical references (p. 57-62).

Thesis (Ph. D.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 208-235).

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 339-368). Also available in print.

Although a substantial amount is known about the pathogenesis of osteoarthrosis, its aetiology and in particular the role that mechanical factors play, remains unclear. One particular hypothesis suggests that cartilage adapts mechanically so that it may transmit, without sustaining damage, the stresses to which it is predominantly subjected, and that damage to the cartilage is caused by infrequent high stresses in excess of the predominant level. As a corollary, it was suggested that highly stressed cartilage should be stiffer than lowly stressed cartilage. A survey of the mechanical properties of normal articular cartilage from unembalmed cadaveric knee and ankle joints was undertaken to test this hypothesis. For this purpose, a specially developed indentation test apparatus was commissioned. Tests of the machine's measurement capabilities indicate that coefficients of variation of 2.14% and 1.20% for indentation and cartilage thickness measurement could be expected. The maximum percentage errors in the calculated creep modulus value which could result from these typical measurement errors, were 4.2% and 2.9% respectively. Creep modulus values, calculated from these measurements, were used in topographical comparisons of cartilage stiffness. The stiffest areas of cartilage in the knee joint were the femoral condyles and areas of the tibia covered by the menisci. Cartilage on the patellar surfaces of the femur and in areas exposed by the menisci was significantly softer. Cartilage from the ankle joint was considerably stiffer than cartilage from the knee. Comparisons between the cartilage stiffness and levels of stress which act in the knee and ankle joints during normal ambulatory activity, showed the stiffest areas of cartilage to be subjected to the greater stresses. Correlations of averaged data values indicated a significant (p < 0.01) direct relationship between cartilage stiffness and stress. This relationship and the consistency with which osteoarthrotic lesions were found in areas subjected to damaging patterns of stress supported the hypothesis under examination. The lack of correlation found between the proteoglycan content and cartilage stiffness suggested that structural rather than compositional factors may be more important in influencing the compressive stiffness of normal articular cartilage.