Pathways to understanding the genomic aetiology of osteoarthritis

Abstract

Osteoarthritis is a common, complex disease with no curative therapy. In this review, we summarize current knowledge on disease aetiopathogenesis and outline genetics and genomics approaches that are helping catalyse a much-needed improved understanding of the biological underpinning of disease development and progression.

Figure 1.

Illustration showing the key pathological features of osteoarthritis. The left side of the image shows the normal knee and the right side shows the diseased joint.

Figure 2.

Established OA loci. Each locus is identified by the nearest gene(s) and coloured black to represent association in both sexes, blue for males only and red for females only. The discovery study population is of European descent unless indicated by an asterisk in which case the population is Asian (BTNL2 was identified in a combined Asian and European analysis).

Figure 3.

Intact and degraded cartilage-bone interface (osteochondral unit). (A) Cartilage/bone interface showing fibrillation and loss of articular cartilage (blue); (B) magnified image showing clustering of chondrocytes in the deeper cartilage layers; (C) magnified image of the cartilage/bone interface showing blood vessels invading the cartilage layer; (D) loss of proteoglycan indicated by loss of Alcian blue staining.

Figure 4.

Functional characterization of loci associated with osteoarthritis. Schema showing an approach to functionally characterize OA-associated variants and candidate target genes using isogenic hiPSC derived chondrocytes (A) and patient hiPSC-derived chondrocytes carrying the selected variant (B).