TitlePotential effects of triterpenoids in osteoarthritis model systems
NameShah, Noopur Snehal (author), Suh, Nanjoo (chair), Conney, Allan H (internal member), Liu, Alice (internal member), Rutgers University, Graduate School - New Brunswick,
SubjectCell and Developmental Biology,
DescriptionOsteoarthritis, a degenerative joint disease, is one of the most common rheumatic disorders and the leading cause of chronic disability in the United States. Currently there are many pharmacologic and non-pharmacologic therapies for osteoarthritis however; these therapies do not appear to concomitantly affect disease symptoms and structure. Here, we have investigated the effects of synthetic oleanane triterpenoids, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), and its analogs CDDO-imidazolide (CDDOIm) and CDDO-ethyl amide (CDDO-EA) in the anabolic as well as catabolic pathways of osteoarthritis using two different osteoarthritis model systems. We found that CDDO-Im and CDDO-EA, at concentrations as low as 200 nM, induce chondrogenesis in organ cultures of new born mouse calvaria in a time and dose dependant manner. The cartilage phenotype was measured histologically with metachromatic toluidine blue staining for proteoglycans and by immunohistochemical staining for type II collagen. Real time PCR analysis using mRNA from calvaria after a 7day treatment with CDDO-Im and CDDO-EA showed upregulation of SOX9 and collagen type 2 and well as other cartilage markers. We also found that LG100268, a rexinoid, downregulates the expression of primary cartilage markers in mouse calvaria suggesting a possible role for rexinoids in chondrogenesis. Vitamin D (1α 25(OH)2 D3) did not show any significant effects at the dose tested. With respect to the catabolic pathway, we established that CDDO-EA and CDDO-Im are involved in suppression of tumor necrosis factor-α (TNF-α) and interleukin 1-β (IL-1β) induced matrix metalloproteinase (MMP) expression in SW1353 chondrosarcoma cells. These results suggest that synthetic triterpenoids CDDO-Im and CDDO-EA can be considered as potentially useful agents for the treatment of osteoarthritis.
NoteIncludes bibliographical references
Noteby Noopur Snehal Shah
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.