Show simple item record

dc.contributor.authorPorter, Ryan Michaelen_US
dc.date.accessioned2014-03-14T20:17:47Z
dc.date.available2014-03-14T20:17:47Z
dc.date.issued2005-10-14en_US
dc.identifier.otheretd-10302005-194237en_US
dc.identifier.urihttp://hdl.handle.net/10919/29403
dc.description.abstract

Articular cartilage functions to reduce the mechanical stresses associated with diarthrodial joint movement, protecting these joints over a lifetime of use. Tissue function is maintained through the balance between synthesis and resorption (i.e., metabolism) of extracellular matrix (ECM) by articular chondrocytes (ACs). Two important hormonal regulators of cartilage metabolism are interleukin-1 (IL-1) and insulin-like growth factor-I (IGF-I). These factors have antagonistic effects on chondrocyte activity, and during the progression of osteoarthritis, IL-1 is thought to promote chondrocyte hyporesponsiveness to IGF-I. To better understand how the anabolic (IGF-I) and catabolic (IL-1) stimuli are linked within articular cartilage, we examined the mechanisms by which IL-1 regulates the IGF-I signaling system of ACs. Equine chondrocytes from non-arthritic stifle joints were multiplied over serial passages, re-differentiated in alginate beads, and stimulated with recombinant equine IL-1b. Chondrocytes were assayed for type I IGF receptor (IGF-IR), IGF binding proteins (IGFBPs), and endogenously-secreted IGF-I. Our experimental findings solidify the significance of IL-1 as a key regulator of IGF-I signaling within articular cartilage, demonstrating that regulation of the IGF-I system occurs through both direct (transcription) and indirect (proteolysis) mechanisms. These results have implications for molecular therapies (e.g., gene transfer) directed at reversing osteoarthritic cartilage deterioration.

The presented research concerns not only cartilage biology but also tissue engineering strategies for cartilage repair. Alginate hydrogel culture has been reported to re-establish chondrocytic phenotype following monolayer expansion, but studies have not addressed effects on the signaling systems responsible for chondrocyte metabolism. We investigated whether chondrocyte culture history influences the IGF-I system and its regulation by IL-1. ACs expanded by serial passaging were either encapsulated in alginate beads or maintained on tissue culture plastic (TCP). Bead and TCP cells were plated at high-density, stimulated with IL-1b, and assayed for expression of IGF-I signaling mediators. Intermediate alginate culture yielded disparate basal levels of IGF-IR and IGFBP-2, which were attributed to differential transcription. The distinct mediator profiles coincided with varied effects of exogenous IL-1b and IGF-I on collagen Ia1 expression and cell growth rate. This study demonstrates that culture strategy impacts the IGF-I system of ACs, likely impacting their capability to mediate cartilage repair.

en_US
dc.publisherVirginia Techen_US
dc.relation.haspartDissertation_Ryan_Porter.pdfen_US
dc.rightsI hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Virginia Tech or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.en_US
dc.subjectarticular chondrocytesen_US
dc.subjectinsulin-like growth factor-I (IGF-I)en_US
dc.subjectosteoarthritisen_US
dc.subjectequineen_US
dc.subjectcell signalingen_US
dc.subjectinterleukin-1 (IL-1)en_US
dc.titleChondrocyte Regulation by IL-I and IGF-I: Interconnection Between Anabolic and Catabolic Factorsen_US
dc.typeDissertationen_US
dc.contributor.departmentChemical Engineeringen_US
dc.description.degreePh. D.en_US
thesis.degree.namePh. D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineChemical Engineeringen_US
dc.contributor.committeechairWilliams, Kimberly Forstenen_US
dc.contributor.committeememberGoldstein, Aaron S.en_US
dc.contributor.committeememberDavis, Richey M.en_US
dc.contributor.committeememberAkers, Robert Michaelen_US
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-10302005-194237/en_US
dc.date.sdate2005-10-30en_US
dc.date.rdate2006-11-18
dc.date.adate2005-11-18en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record