The objective was to compare the effects of three corticosteroids at various equimolar concentrations on equine articular explant co-cultures in an inflammatory environment. Synovial and osteochondral explant co-cultures from 6 equine cadavers were exposed to IL-1β (10 ng/mL) and various concentrations (10-4, 10-7, or 10-10 M) of MPA, TA, IPA. Concentrations of PGE2, MMP-13, LDH, and GAG in media were determined at 48 and 96 hours. Results indicated wells with low concentrations of MPA (10-7 and 10-10 M at 48 and 96 hours), TA (10-7 M at 48 hours and 10-7 and 10-10 M at 48 and 96 hours), and IPA (10-10 M at 48 hours) had significantly less PGE2 than positive control samples. Groups with low concentrations (10-7 and 10-10 M) of MPA and TA had significantly less PGE2 than the highest concentration (10-4 M) at 48 hours. Significantly less MMP-13 was detected for all concentrations of MPA, TA, and IPA at 96 hours. The LDH assay results indicated cytotoxicity only for samples treated with IPA at 10-4 M at 48 and 96 hours. GAG was significantly lower for samples treated with TA 10-7 M at 48 hours and MPA 10-10 M at 96 hours versus positive controls. These findings suggest corticosteroids at low concentrations mitigated the inflammatory and catabolic effects of IL-1β to a greater extent than high concentrations. Effects of IPA and MPA were similar to TA at clinically relevant low equimolar concentrations. / Master of Science / Recent data suggest that isoflupredone acetate is commonly administered intra-articularly for treatment of joint disease (osteoarthritis) in horses. Although much data has been published regarding effects of other corticosteroids on cartilage, to our knowledge there have been no similar studies of the effects of isoflupredone acetate. With increased scrutiny from the general public and more stringent control of medication use by regulatory agencies, determination of information regarding such common intra-articular therapies is imperative. In addition, prior studies have only evaluated the effects of corticosteroids on cartilage, whereas other joint tissues (subchondral bone and synovium) have been shown to be important to the biological responses of joints. Therefore, to more closely simulate the natural joint environment, this study was conducted with a co-culture model incorporating synovial tissue, articular cartilage, and subchondral bone within an inflammatory environment (via stimulation with interleukin-1β). The effects of various concentrations of methylprednisolone acetate, triamcinolone acetonide, and isoflupredone acetate on joint tissues were determined via measurement of selected biomarkers. This study provided the first data regarding biological effects of IPA on joint tissues of horses, and the first comparison of such effects with those of other corticosteroids commonly used intra-articularly for the treatment of joint disease in horses.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/83501 |
| Date | 08 June 2018 |
| Creators | Trahan, Richard Angellas |
| Contributors | Biomedical and Veterinary Sciences, Byron, Christopher R., Dahlgren, Linda A., Pleasant, R. Scott |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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