Thesis (DTech. degree in Biomedical Sciences)--Tshwane University of Technology, 2009. / Damaged articular cartilage requires tissue engineering based therapeutic methods because of its minimal self-repair capacity. Articular cartilage is a heterogeneous avascular, aneural tissue that provides a smooth bearing surface for movement. It consisting of superficial, middle, and deep layers with varying matrix composition. The superficial zone is the site of superficial zone protein synthesis that functions as a boundary lubricant. The middle and deep layers abound in collagen II and proteoglycan aggrecan. Since articular cartilage consists of zones that are specific in their functions, the replication of these zones may be important in obtaining a functional tissue-engineered construct. Understanding the differences in gene expression between these layers is necessary for tissue engineering. The aim of the study is to use bone morphogenetic proteins (BMPs) and growth factor morphogens that may help in the regeneration and repair of articular cartilage through stimulation of chondrocyte proliferation and differentiation. The role of various transforming growth factor beta (TGF-)/Bone morphogenetic proteins (BMPs) superfamily on expression of the following proteins: cartilage oligomeric matrix protein (COMP), superficial zone protein (SZP), cartilage intermediate layer protein (CILP), SRY-related (sex determining region Y)-sox 9 (SOX 9), aggrecan (AGG) and collagen type II from three distinct zones of cartilage (superficial, middle and deep) was investigated. It is hypothesized that the chondrocytes from the superficial, middle, and deep zone of articular cartilage would have different rates of proliferation and biosynthetic activity, and that these proteins would respond differently when treated with the (TGF-)/ bone morphogenetic proteins (BMPs) superfamily. Stifle joints (n=28) from three month-old calves were obtained from a local abattoir. Articular chondrocytes were isolated from three distinct zones of cartilage and cultured as monolayers in a serum-free chemically defined medium. The results are presented as the mean and standard deviations for each experiment. A one way analysis of variance (ANOVA) with Tukey’s HSD (Honestly Significant Differences) to account for multiple comparisons was used to determine the effects TGF- _1, BMP-7, GDF-5, and Activins A, B and AB isoforms on COMP, SZP, CILP, aggrecan, sox 9 and collagen type II accumulation in different zones of articular cartilage. A significance level of p < 0.05 was used to determine the difference between the control and treated cells and p < 0.01 the dose-dependence of morphogens within the zones. Accumulation of COMP, SZP, CILP, aggrecan, sox 9 and collagen type II in culture medium in response to various members of the BMP/TGF-_ superfamily was determined by enzyme-linked immunosorbent assay (ELISA) and messenger ribonucleic acid (mRNA) by quantitative real-time PCR. TGF-_1 significantly stimulated the expression of COMP and SZP at the mRNA and protein level in the superficial zone in a time- and dosage- dependent manner, CILP at the mRNA in the middle zone, aggrecan, sox 9 and collagen type II at the mRNA in the middle and deep zone. An unexpected discovery was that the superficial chondrocytes were more responsive to morphogens than the deeper layers. BMP-7 and growth differentiation factors (GDF-5) also up-regulate COMP, SZP, CILP, aggrecan and collagen type II expression, although the effects were not as potent as with TGF-_1. Activins A, B and AB demonstrated no effects on all the genes accumulation in all zones. In conclusion, TGF-_, BMP-7 and GDF-5 are important regulators of different genes in different zones of articular cartilage.

Thesis supervisor: Marcelo B. Soares. Includes separate files (Appendix A-E) for thesis supplements. Includes bibliographic references (p. 102-115).

Thesis (Ph. D.)--University of Missouri--Columbia, 1998. / "December 1998" Typescript. Vita. Includes bibliographical references (l. 132). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri--Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaf 132). Also available on the Internet.

No description available.

Thesis (Ph. D.)--University of Hong Kong, 2006.

No description available.

Thesis (Ph.D.)--University of Delaware, 2006. / Principal faculty advisor: Andras Z. Szeri, Dept. of Mechanical Engineering. Includes bibliographical references.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1988. / Vita. Abstract. Includes bibliographical references (leaves 116-125). Also available via the Internet.

Thesis (doctoral)--Freie Universität Berlin, 1980.