Dissertation/Thesis Abstract

The Role of Fibroblast Growth Factor Receptor 3 In Growth Plate Chondrocytes
by Smith, Logan Blair, Ph.D., University of California, Davis, 2010, 95; 3427483
Abstract (Summary)

Tall stature in humans is commonly associated with cultural status and privilege. Larger skeletal frame size in food animals is valued because genetic size scaling suggests it may improve growth efficiency and carcass characteristics. The cellular activity of proliferation, hypertrophy, and matrix production at the bone growth plate is the basis for endochondral long bone growth. Because chondrocyte proliferation at the growth plate is the greatest factor driving bone elongation the rate of proliferation can be a major determinant in mature skeletal size. Therein, understanding regulators of chondrocyte proliferation will shed light on the bone elongation process.

Much of what is known about bone growth regulation stems from analysis of extracellular factors such as hormones. However, the intracellular mechanisms transducing these extracellular signals is less well understood. In the epiphyseal growth plate, fibroblast growth factor receptor 3 (FGFR3) is a major negative regulator of long bone growth. Point mutations in FGFR3 account for skeletal size differences in humans, mice and sheep. Dogs offer a unique model to study regulators of skeletal size differences, such as FGFR3, since they exhibit the greatest variation in skeletal size of any species. The objectives of this study were to characterize the role of FGFR3 mutations in determining mature skeletal size in and to examine molecular regulatory mechanisms that mediate FGFR3 regulation of bone growth. Specifically, the hypothesis addressed for the initial study was that SNPs in the FGFR3 gene sequence accounted for divergent skeletal sizes in dogs. The hypothesis for the final study was that FGFR3 exerted its inhibitory effects on chondrocyte growth by inhibiting the expression of telomerase, a key enzyme determining proliferation versus senescence profiles in cell lineages. Our results may further elucidate factors responsible for skeletal frame size variation in dogs and for intracellular mechanisms involved in growth plate chondrocyte proliferation rate, senescence, and maturation.

Indexing (document details)
Advisor: Oberbauer, Anita M.
Commitee: Delany, Mary E., Yellowley, Clare
School: University of California, Davis
Department: Molecular, Cellular and Integrative Physiology
School Location: United States -- California
Source: DAI-B 71/12, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Genetics, Physiology
Keywords: Bone, Chondrocytes, Epiphyseal growth plates, FGFR3, Proliferation, Telomerase
Publication Number: 3427483
ISBN: 9781124319407
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