Abstract/Details

The roles of the Rho GTPase protein Rac-1 in cell morphology and function during chondrocyte maturation


2008 2008

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Abstract (summary)

The objective of this dissertation was to determine the roles of Rac-1 in the regulation of chondrocyte morphology, the remodeling of the extracellular matrix and the expression of a mature phenotype. We established a replication competent, retroviral system to modulate Rac-1 activity in primary chick chondrocytes. The results of Specific Aim 1 indicated that Rac-1 activation induced cell enlargement and development of actin filamentation, which are associated with chondrocyte hypertrophy. Conversely, cells expressing inactive Rac-1 had a rounded morphology with a less developed actin architecture, comparable to immature chondrocytes. In Specific Aim 2, we determined that Rac-1 inactivation maintained an immature phenotype as shown by high proteoglycan accumulation and increased expression of aggrecan and collagen type IX. Conversely, Rac-1 activation upregulated the expression of hypertrophic markers: alkaline phosphatase activity and matrix metalloproteinase expression. Thus, the activation status of Rac-1 correlated with the maturation status of chondrocytes. The data presented in Specific Aim 3 described the activity and localization of Rac-1 during chondrocyte maturation. We demonstrated that Rac-1 activity increased in mature chondrocytes when compared to immature cells. In addition, Rac-1 tagged with GFP co-localized with F-actin at the cortical membrane. Further, these proteins identically altered their distribution in response to treatment with Wnt3A, a factor known to induce maturation in chondrocytes. In addition, cooperation between Rac-1 activation and Wnt signaling was suggested by the findings that Wnt3A stimulated Rac-1 activation and that morphological changes induced by Wnt3A required Rac-1 activation. In conclusion, the results of this investigation indicated that Rac-1 activation induces the expression of a mature, hypertrophic-like phenotype, while chondrocytes under Rac-1 inactivation retain an immature phenotype. Further, our data implies that Rac-1 controls actin organization and cell morphology in chondrocytes. Hence, the data presented in this dissertation reveal that Rac-1 has important roles in the regulation of the hypertrophic phenotype and the cytoskeletal organization of chondrocytes during endochondral ossification.

Indexing (details)


Subject
Cellular biology;
Biomedical engineering
Classification
0379: Cellular biology
0541: Biomedical engineering
Identifier / keyword
Applied sciences, Biological sciences, Actin, Chondrocytes, Growth plates, Hypertrophy, Rho GTPase
Title
The roles of the Rho GTPase protein Rac-1 in cell morphology and function during chondrocyte maturation
Author
Kerr, Bethany Amber
Number of pages
153
Publication year
2008
Degree date
2008
School code
0272
Source
DAI-B 73/01, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781124952758
University/institution
Thomas Jefferson University
University location
United States -- Pennsylvania
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3480611
ProQuest document ID
899274287
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/899274287
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