The Effects of 17-alpha Estradiol on Osteoarthritis and Bone Development in Genetically Heterogeneous Het3 Mice
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Date
2024-05
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The Ohio State University
Abstract
Osteoarthritis (OA) is a common degenerative disease of the joints, typically in the knee, and is caused by the joint’s articular cartilage. When damaged, osteophytes and increased subchondral bone growth results in pain and limits range of motion. Current therapies often are not very effective and surgical therapies are invasive and often require revisions. More effective, noninvasive, and longer lasting treatments are needed. 17-alpha is a non-feminizing isoform of estrogen that has been found to improve lifespan in male mouse models, as well as improve age related conditions like insulin sensitivity, obesity, and inflammation. 17-alpha has recently been studied for its impact on OA in Het3 mice and was found to have a minimal impact, but this study only included mice equivalent to an 85-year-old human. It would be advantageous to investigate the effects of 17-alpha throughout the aging process at different time points. We hypothesized that 17-alpha administration to Het3 males would slow age-related declines in bone and joint health when compared to the control. Mice were fed 17-alpha in standard chow 19 weeks prior to euthanasia at 70 and 105 weeks for the middle and old groups, respectively. Controls were euthanized at 25±6 weeks (young), 63±9 weeks (middle), 104±3 weeks (old). Three dimensional renderings of the samples’ microCT scans were blinded and scored using the Kellgren-Lawrence classification system (0 = healthy, 4 = severe OA). Qualitative microCT assessed five volumes of interest in close proximity to the joint. Blinded grading found increased scores with age among the controls and a reduced OA score of the old treated group versus the old control group. MicroCT analysis indicated minimal significant differences between groups in any volume of interest. However, BV and TV did increase in middle-aged treated mice compared to the respective control in the medial tibial plateau. This may indicate osteophytic bone growth. Improvement in OA score for old treated mice may indicate protective effects of 17-alpha more than middle-aged mice. However, given the small sample size of treated mice (n = 4 middle, n = 2 old) more data needs to be collected to further validate their findings. More samples are to be analyzed and histological analysis will be performed on all samples.
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Keywords
Osteoarthritis, 17-alpha estradiol, microCT, Het3, Knee