Objectives A functional polymorphism leading to reduced levels of growth and differentiation factor 5 (GDF5) was recently identified as a susceptibility factor for osteoarthritis. The authors studied the potential mechanisms of GDF5 involvement in osteoarthritis using haploinsufficient Gdf5Bp-J/+ mice.
Methods Gdf5Bp-J/+ mice were challenged in the collagenase-induced arthritis model, the medial meniscus destabilisation model, the papain-induced arthritis model and a treadmill running model. Bone density and subchondral bone parameters were determined using dual energy x-ray absorptiometry and peripheral quantitative CT. Additional in-vitro and ex-vivo analyses studied cartilage metabolism, gait and collagen characteristics.
Results Gdf5Bp-J/+ mice appeared phenotypically normal. No difference in osteoarthritis severity was found in the different models, with the exception of increased synovial hyperplasia in the joints of Gdf5Bp-J/+ mice in the treadmill model. However, in the collagenase-induced model severe joint damage was found in the contralateral joints of Gdf5Bp-J/+ mice. Gait analysis demonstrated an aberrant walking pattern in Gdf5Bp-J/+ mice. In addition, Gdf5Bp-J/+ mice have a decreased subchondral bone density and a distorted arrangement of collagen fibres in bone.
Conclusions These data suggest that decreased GDF5 levels in mice can contribute to osteoarthritis development by different mechanisms including altered loading and subchondral bone changes. This highlights the importance of the joint as an organ with different tissues involved in joint disease.
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Funding This work is funded by a grant from Coordination Theme 1 (Health) of the European Community's FP7, grant agreement number HEALTH-F2-2008-00 (large collaborative project TREAT-OA) and by a GOA grant from Katholieke Universiteit Leuven, Leuven. MD is the recipient of a doctoral fellowship from the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT Vlaanderen). RJUL is the recipient of a postdoctoral fellowship from the Research Foundation, Flanders (FWO Vlaanderen).
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.