Browsing by Author "Francis, Destiny"

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    The Natural History of Bone Marrow Lesions and Cysts in the Dunkin-Hartley Guinea Pig Knee Osteoarthritis Model
    (2020-10-14) Francis, Destiny; Manske, Sarah Lynn; Matyas, John Robert; Dunn, Jeff F.
    Idiopathic knee osteoarthritis (OA) is a disease with unknown etiology, where age is described as a major risk factor. There is a need to document OA's natural history to gain insight into its etiology. Therefore, an animal model like the Dunkin-Hartley (DH) guinea pig that spontaneously develops a knee OA phenotype similar to idiopathic OA observed in humans can be used to study the disease-related bony degeneration. This phenotype includes osteophyte formation, sclerosis, bone marrow lesions (BMLs), and cysts within a relatively short period. This thesis employs advanced magnetic resonance imaging (MRI), micro-computed tomography (μCT), and histological techniques to assess knee joint degeneration in DH guinea pigs at ages 2, 4, 6, 12, and 24 months. The results from this project show evidence of cartilage degradation and bone cyst formation in the 6-month age group, which becomes more apparent in the 12 and 24-month age groups. When present, cysts were primarily located in the central compartment of the bone and often accompanied by osteophytes and sclerosis. Joint degeneration was most severe in the 24-month age group with the largest cysts as well as the greatest osteophyte size and number. Bone microarchitecture was also significantly affected in this age group. Overall femoral and tibial trabecular number (Tb.N) was lowest in the 24-month age group, and it had the highest medial femoral subchondral bone plate thickness (Sbp.Th), femoral and tibial subchondral bone plate porosity (Sbp.Po), femoral trabecular separation (Tb.Sp), and medial tibial trabecular thickness (Tb.Th). The medial compartment also revealed greater joint degeneration, as demonstrated by greater femoral and tibial Sbp.Th and femoral Sbp.Po in the 12 and 24-month age groups compared with the lateral compartment. This project demonstrates that age-related joint degeneration occurs in the DH guinea pig spontaneous knee OA model with evidence of osteophytes, cysts, and bone microarchitecture alterations in older age groups. Although histology revealed abnormalities in the bone that have been associated with MRI-defined BMLs, I am unable to conclude whether or not BMLs occur in this model as a further investigation with MRI is still required.