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Preventive and Osteoarthritis Suppressive Effects of Peretinoin

Ahmad, Nashrah
http://rave.ohiolink.edu/etdc/view?acc_num=kent1602519541029131

Abstract Details

2020, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Osteoarthritis (OA) is one of the leading causes of disability and is caused by a combination of mechanical and biochemical factors. Accumulating evidence suggests that inflammation has a key role in the pathogenesis of OA, and nitric oxide (NO) is considered as one of the major inflammatory mediators in OA that drives many pathological changes during the development and progression of OA. Excessive production of NO in chondrocyte promotes cartilage destruction and cellular injury, and its synthesis in chondrocytes is catalyzed by inducible nitric oxide synthase (iNOS), which is thereby an attractive therapeutic target for the treatment of OA. A number of direct and indirect iNOS inhibitors, bioactive compounds, and plant-derived small molecules have been shown to exhibit a chondroprotective effect by suppressing the expression of iNOS. Currently, there is no effective disease-modifying drug available for OA. Small molecules have proved to be powerful tools for modulating important molecular pathways in development and disease. Our preliminary screening of selected small molecules led us to select imperatorin (IMP) and peretinoin (PRT), which exhibit anti-inflammatory properties; however, their effect in chondrocytes is unknown. IMP is a plant-derived compound, while PRT is an acyclic retinoid and is currently in clinical trials for its efficacy to treat hepato-carcinoma. We found that IMP, as well as PRT, inhibited IL-1β induced expression of iNOS and production of NO in primary human OA chondrocytes by modulating the activation of mitogen-activated protein kinase (MAPK) pathway. Additionally, PRT inhibited matrix degradation by suppressing the expression of matrix metalloproteinase-13 (MMP-13). The work described in this dissertation demonstrates that PRT inhibits the expression of iNOS and production of NO in primary human OA chondrocytes and cartilage explants, identifies the mechanism, and shows OA suppressive effects in a mouse OA model.
Tariq Haqqi (Advisor)
Fayez Safadi (Committee Member)
Moses Oyewumi (Committee Member)
Mohammad Ansari (Committee Member)
Christine Crish (Committee Member)
150 p.
Biomedical Research
Osteoarthritis; inflammation; imperatorin; peretinoin; cartilage; iNOS; nitric oxide

Recommended Citations

Citations

  • Ahmad, N. (2020). Preventive and Osteoarthritis Suppressive Effects of Peretinoin [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1602519541029131

    APA Style (7th edition)

  • Ahmad, Nashrah. Preventive and Osteoarthritis Suppressive Effects of Peretinoin. 2020. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1602519541029131.

    MLA Style (8th edition)

  • Ahmad, Nashrah. "Preventive and Osteoarthritis Suppressive Effects of Peretinoin." Doctoral dissertation, Kent State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=kent1602519541029131

    Chicago Manual of Style (17th edition)

kent1602519541029131
153
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This open access ETD is published by Kent State University and OhioLINK.