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
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
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DOI：
10.1136/ard.2005.045971
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发表时间：
2006-11-01
影响因子：
27.4
通讯作者：
van den Berg, W. B.
中科院分区：
文献类型：
--
作者：
Davidson, E. N. Blaney;Vitters, E. L.;van den Berg, W. B.
背景：骨关节炎的主要特征是软骨损失。此外，经常可以观察到骨赘。转化生长因子 - β (TGF β) 已被认为与防止骨赘中出现的软骨损伤和新软骨形成有关。 目的：研究实验性骨关节炎中的 TGF β 和 TGF β 信号传导，以深入了解 TGF β 在骨关节炎期间软骨降解和骨赘形成中的作用 方法：对小鼠膝关节的组织切片进行免疫组织化学染色，检测 TGF β 3 和磷酸化 SMAD-2 (SMAD-2P)。在两种小鼠骨关节炎模型中研究了表达模式，分别代表自发性骨关节炎（STR/ort 模型）和不稳定性相关骨关节炎（胶原酶诱导的不稳定性模型）。结果：在两种模型的骨关节炎进展过程中，软骨中的 TGF β 3 和 SMAD-2P 染色逐渐减少。严重受损的软骨 TGF beta 3 呈阴性。相反，骨形态发生蛋白 2 (BMP-2) 表达增加。在骨赘形成之前的软骨细胞簇中，TGF β 3 和 SMAD-2P 强烈表达。在早期骨赘中，TGFβ3 存在于外纤维层、外周成软骨细胞和核心中。晚期骨赘仅在纤维层表达TGFβ3。 SMAD-2P 遍布各个阶段的骨赘。在晚期骨赘中，BMP-2强烈表达。结论：数据显示TGFβ3的缺乏与软骨损伤有关，表明在骨关节炎进展过程中TGFβ3的保护作用丧失。此外，我们的结果表明 TGF beta 3 参与早期骨赘发育，而 BMP 可能参与晚期骨赘发育。
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.