Overexpression of active TGF-beta-1 in the murine knee joint: evidence for synovial-layer-dependent chondro-osteophyte formation.
OBJECTIVE
To investigate the impact of a prolonged and constant active TGF-beta expression by the synovial lining cells on cartilage and ligamentous joint structures in vivo.


METHODS
An adenoviral vector (AdTGF-beta1(223,225)) was used for the overexpression of active TGF-beta1 in knee joints of C57Bl/6 mice.


RESULTS
It was found that physiological relevant levels of active TGF-beta1 produced by the synovial lining layer resulted in histopathological changes: hyperplasia of synovium and chondro-osteophyte formation at the so-called chondro-synovial junctions. No histological changes were seen after intra-articular injection of an empty control vector (AdDL70-3) or by overexpression of latent TGF-beta1 (AdTGF-beta1). The predominant site of TGF-beta production in osteoarthritis (OA) and rheumatoid arthritis (RA) is the synovial lining layer. To address the question whether the TGF-beta-induced changes were related to the expression site in the synovial lining, the synovial lining layer was depleted by local treatment with liposomes encapsulating clodronate. Depletion of the lining resulted in a dramatic change of TGF-beta1-induced pathology: markedly reduced chondro-osteophyte formation and increased accumulation of extracellular matrix in the synovium.


CONCLUSIONS
This study shows that overexpression of active TGF-beta1 in the knee joint results in OA-like changes and suggests the synovial lining cells contribute to the chondro-osteophyte formation.
Department of Rheumatology, University Hospital Nijmegen, 6525 GA, The Netherlands. a.bakker@reuma.azn.nl
A C
AC
Bakker
F A
FA
van de Loo
H M
HM
van Beuningen
P
P
Sime
P L
PL
van Lent
P M
PM
van der Kraan
C D
CD
Richards
W B
WB
van den Berg
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology; D006614:Hindlimb; D007596:Joints / Q000378:metabolism*; D008023:Ligaments, Articular / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta; D004002:Clodronic Acid