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Expression of transforming growth factor-ß (TGFß) and the TGFß signalling molecule SMAD-2P in spontaneous and instability-induced osteoarthritis: role in cartilage degradation, chondrogenesis and osteophyte formation

Experimental Rheumatology and Advanced Therapeutics, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands

Correspondence to:
Correspondence to:
P M van der Kraan
Experimental Rheumatology and Advanced Therapeutics, Radboud University Medical Centre, Geert Grooteplein 26-28, 6525 GA Nijmegen, The Netherlands;p.vanderkraan{at}reuma.umcn.nl

Background: The primary feature of osteoarthritis is cartilage loss. In addition, osteophytes can frequently be observed. Transforming growth factor-ß (TGFß) has been suggested to be associated with protection against cartilage damage and new cartilage formation as seen in osteophytes.

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

Methods: Histological sections of murine knee joints were stained immunohistochemically for TGFß3 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: TGFß3 and SMAD-2P staining was increasingly reduced in cartilage during osteoarthritis progression in both models. Severely damaged cartilage was negative for TGFß3. In contrast, bone morphogenetic protein-2 (BMP-2) expression was increased. In chondrocyte clusters, preceding osteophyte formation, TGFß3 and SMAD-2P were strongly expressed. In early osteophytes, TGFß3 was found in the outer fibrous layer, in the peripheral chondroblasts and in the core. Late osteophytes expressed TGFß3 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.

Conclusion: Data show that lack of TGFß3 is associated with cartilage damage, suggesting loss of the protective effect of TGFß3 during osteoarthritis progression. Additionally, our results indicate that TGFß3 is involved in early osteophyte development, whereas BMP might be involved in late osteophyte development.

Abbreviations: BMP-2, bone morphogenetic protein-2; ECM, extracellular matrix; TGF-ß, transforming growth factor-ß