Expression of transforming growth factor-β (TGFβ) and the TGFβ 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 (TGF beta) has been suggested to be associated with protection against cartilage damage and new cartilage formation as seen in osteophytes. Objective: To study TGF beta and TGF beta signalling in experimental osteoarthritis to gain insight into the role of TGF beta in cartilage degradation and osteophyte formation during osteoarthritis progression. Methods: Histological sections of murine knee joints were stained immunohistochemically for TGF beta 3 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: TGF beta 3 and SMAD-2P staining was increasingly reduced in cartilage during osteoarthritis progression in both models. Severely damaged cartilage was negative for TGF beta 3. In contrast, bone morphogenetic protein-2 (BMP-2) expression was increased. In chondrocyte clusters, preceding osteophyte formation, TGF beta 3 and SMAD-2P were strongly expressed. In early osteophytes, TGF beta 3 was found in the outer fibrous layer, in the peripheral chondroblasts and in the core. Late osteophytes expressed TGF beta 3 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 TGF beta 3 is associated with cartilage damage, suggesting loss of the protective effect of TGF beta 3 during osteoarthritis progression. Additionally, our results indicate that TGF beta 3 is involved in early osteophyte development, whereas BMP might be involved in late osteophyte development.