Research ArticleOsteoarthritis

Topographic modeling of early human osteoarthritis in sheep

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Science Translational Medicine  04 Sep 2019:
Vol. 11, Issue 508, eaax6775
DOI: 10.1126/scitranslmed.aax6775

Deciphering degeneration

Aging and injury are known to contribute to osteoarthritis, a disease characterized by the breakdown of cartilage. Here, Oláh et al. induced meniscal injury in sheep and created detailed maps of disease progression. They found that cartilage and bone breakdown occurred first in the injured region before spreading throughout the joint. Patterns of degeneration observed in the sheep 6 months after injury mirrored pathology observed in human osteoarthritis. This large animal model of osteoarthritis could be useful for furthering our understanding of disease progression and for testing potential therapies.

Abstract

Articular cartilage damage occurring during early osteoarthritis (OA) is a key event marking the development of the disease. Here, we modeled early human OA by gathering detailed spatiotemporal data from surgically induced knee OA development in sheep. We identified a specific topographical pattern of osteochondral changes instructed by a defined meniscal injury, showing that both cartilage and subchondral bone degeneration are initiated from the region adjacent to the damage. Alterations of the subarticular spongiosa arising locally and progressing globally disturbed the correlations of cartilage with subchondral bone seen at homeostasis and were indicative of disease progression. We validated our quantitative findings against human OA, showing a similar pattern of early OA correlating with regions of meniscal loss and an analogous late critical disturbance within the entire osteochondral unit. This translational model system can be used to elucidate mechanisms of OA development and provides a roadmap for investigating regenerative therapies.

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