Expression of transforming growth factor-beta (TGFbeta) and the TGFbeta signalling molecule SMAD-2P in spontaneous and instability-induced osteoarthritis: role in cartilage degradation, chondrogenesis and osteophyte formation.
BACKGROUND
The primary feature of osteoarthritis is cartilage loss. In addition, osteophytes can frequently be observed. Transforming growth factor-beta (TGFbeta) has been suggested to be associated with protection against cartilage damage and new cartilage formation as seen in osteophytes.


OBJECTIVE
To study TGFbeta and TGFbeta signalling in experimental osteoarthritis to gain insight into the role of TGFbeta in cartilage degradation and osteophyte formation during osteoarthritis progression.


METHODS
Histological sections of murine knee joints were stained immunohistochemically for TGFbeta3 and phosphorylated SMAD-2 (SMAD-2P). Expression patterns were studied in two murine osteoarthritis models, representing spontaneous (STR/ort model) and instability-associated osteoarthritis (collagenase-induced instability model).


RESULTS
TGFbeta3 and SMAD-2P staining was increasingly reduced in cartilage during osteoarthritis progression in both models. Severely damaged cartilage was negative for TGFbeta3. In contrast, bone morphogenetic protein-2 (BMP-2) expression was increased. In chondrocyte clusters, preceding osteophyte formation, TGFbeta3 and SMAD-2P were strongly expressed. In early osteophytes, TGFbeta3 was found in the outer fibrous layer, in the peripheral chondroblasts and in the core. Late osteophytes expressed TGFbeta3 only in the fibrous layer. SMAD-2P was found throughout the osteophyte at all stages. In the late-stage osteophytes, BMP-2 was strongly expressed.


CONCLUSIONS
Data show that lack of TGFbeta3 is associated with cartilage damage, suggesting loss of the protective effect of TGFbeta3 during osteoarthritis progression. Additionally, our results indicate that TGFbeta3 is involved in early osteophyte development, whereas BMP might be involved in late osteophyte development.
Blaney Davidson
E N
EN
Experimental Rheumatology and Advanced Therapeutics, Radboud University Medical Centre, Geert Grooteplein 26-28, 6525 GA Nijmegen, The Netherlands.
Vitters
E L
EL
van der Kraan
P M
PM
van den Berg
W B
WB
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D020219:Chondrogenesis; D018450:Disease Progression; D007593:Joint Instability / Q000150:complications; D008297:Male; D051379:Mice; D009999:Ossification, Heterotopic / Q000378:metabolism; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053782:Transforming Growth Factor beta3
D051899:Smad2 Protein; C497783:Smad2 protein, mouse; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3