期刊
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
卷 52, 期 -, 页码 53-57出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2016.02.020
关键词
Fundamental disease; Rare disease; Alkaptonuria; Osteoarthritis; Exposed collagen hypothesis; High density mineralised protrusions (HDMPs); Trabecular excrescences
资金
- Rosetrees Foundation
- Childwick Trust
- Big Lottery
- EUFP7
Fundamental diseases is a term introduced by the charity Findacure to describe rare genetic disorders that are gateways to understanding common conditions and human physiology. The concept that rare diseases have important lessons for biomedical science has been recognised by some of the great figures in the history of medical research, including Harvey, Bateson and Garrod. Here we describe some of the recently discovered lessons from the study of the iconic genetic disease alkaptonuria (AKU), which have shed new light on understanding the pathogenesis of osteoarthritis. In AKU, ochronotic pigment is deposited in cartilage when collagen fibrils become susceptible to attack by homogentisic acid (HGA). When HGA binds to collagen, cartilage matrix becomes stiffened, resulting in the aberrant transmission of loading to underlying subchondral bone. Aberrant loading leads to the formation of pathophysiological structures including trabecular excrescences and high density mineralised protrusions (HDMPs). These structures initially identified in AKU have subsequently been found in more common osteoarthritis and appear to play a role in joint destruction in both diseases. (C) 2016 Elsevier Ltd. All rights reserved.
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