This paper reports on a proof of concept project funded by the UK National Council for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), with the aim of developing an in vitro model to recapitulate the human osteoarthritic joint, based on a multiple human cell type co-culture system, for research and drug development in OA. The targets were: (i) the development of a cell culture platform that could produce a mixed stable cell culture of cell types that represent the key components of the human joint: synoviocytes – type I and type II; osteoblasts; osteoclasts; chondrocytes/cartilage or cartilage-like matrix; adipocytes; and immune cells. (ii) demonstration of cell phenotype stability and viability for at least 72 hours. In order to establish the cell culture platform we have developed an eight-channel cell printer, capable of accurately and reliably printing the required cell types to create osteochondral and synovial cell types within a transwell system. Two different sets of cells have been developed and processed using the cell printer: a set based on using an immortalised hTERT MSC line to create osteoblasts, chondrocytes and adipocytes, with commercial cells lines providing the other cell types, and a set obtained from tissue excised during orthopaedic surgery. This gives both a repeatable set of cells with which to undertake mode of action studies, and a bank of cell sets which will be representative of different stages of osteoarthritis. The co-cultures have been immunohistochemically assessed in order to demonstrate maintenance of phenotype.

From a prospective, cross-sectional survey of 402 patients who had a total hip (THR) or a total knee (TKR) replacement for idiopathic osteoarthritis (OA) at a major centre, we determined the prevalence of these replacements for idiopathic OA in their 1171 siblings and 376 spouses. Using spouses as controls, the relative risk of THR in siblings was 1.86 (95% CI 0.93 to 3.69). The relative risk for TKR in siblings v spouses was 4.8 (95% CI 0.64 to 36.4) whereas the risk for the combined outcome measure of THR or TKR was 2.32 (95% CI 1.22 to 4.43) when siblings and spouses over 64 years of age were compared. Using a threshold liability model (Falconer), the heritability of end-stage OA of the hip was estimated at 27%.

The increased risks of joint replacement for severe, idiopathic OA which we found in siblings suggest that genetic influences are important in end-stage OA of the hip and knee.