Characterization of Osteochondritis Dissecans and Development of a Small Animal Model of its Progression

PI’s: Clifton Willimon & Robert Guldberg

Osteochondritis Dissecans (OCD) of the knee is an incresingly common condition that predominantly affects adolescent and young adults,and progresses to early onset osteoarthritis. OCD initially involves the formation of an avascular lesion in the subchondral bone withsecondary effects in the overlaying articular cartilage. During late stages of this disorder, the lesion becomes unstable and separation of anosteochondral fragment ensues. The etiology of OCD is not fully understood, and previous research has been primarily limited to retrospective clinical studies, this hampering the creation of novel therapeutics. Furthermore, current preclinical animal models replicate only late stages of OCD, and their utility in the field is limited. It is the failure to treat OCD in its early stages that results in the progression of this disorder and the onset of osteoarthritis at an early age. Therefore, a new preclinical model is needed such that the disease progression mechanisms can be more fully investigated, with a view to developing and testing new therapeutic interventions.

The overall objective of this proposal is to develop a small preclinical animal model in order to better tailor diagnosis and treatment of this musculoskeletal disorder. The central hypothesis of this proposal is that the animal model will replicate early stages of OCD and its progression and will be advantageous in testing the efficacy and outcomes of current clinical procedures. We will achieve our objective by inducing chemical necrosis in the bone near the subchondral area, which will yield an osteonecrotic lesion with intact overlaying cartilage; mimicking stages 1 and 2 of OCD. We will also evaluate the therapeutic benefits of cell delivery coupled with marrow stimulation techniques (current clinical practice) in the anima model, in order to prove its utility within the field.

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