GDF5 deficiency in mice is associated with instability-driven joint damage, gait and subchondral bone changes.
OBJECTIVE
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 Gdf5(Bp-J/+) mice.


METHODS
Gdf5(Bp-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
Gdf5(Bp-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 Gdf5(Bp-J/+) mice in the treadmill model. However, in the collagenase-induced model severe joint damage was found in the contralateral joints of Gdf5(Bp-J/+) mice. Gait analysis demonstrated an aberrant walking pattern in Gdf5(Bp-J/+) mice. In addition, Gdf5(Bp-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.
Daans
Melina
M
Department of Musculoskeletal Sciences, Division of Rheumatology, Laboratory for Skeletal Development and Joint Disorders, Katholieke Universiteit Leuven, Leuven, Belgium.
Luyten
Frank P
FP
Lories
Rik J U
RJ
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology* / Q000235:genetics; D015519:Bone Density / Q000502:physiology; D002358:Cartilage, Articular / Q000378:metabolism; D017364:Collagenases; D055428:Growth Differentiation Factor 5 / Q000172:deficiency* / Q000235:genetics; D057895:Haploinsufficiency; D007593:Joint Instability / Q000209:etiology* / Q000235:genetics; D007794:Lameness, Animal / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008817:Mice, Mutant Strains; D009043:Motor Activity; D010003:Osteoarthritis / Q000209:etiology* / Q000235:genetics; D010206:Papain
C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D010206:Papain; D017364:Collagenases