Dickkopf-1 is a master regulator of joint remodeling
Dickkopf-1 is a master regulator of joint remodeling
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DOI：
10.1038/nm1538
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发表时间：
2007-02-01
期刊：
影响因子：
82.9
通讯作者：
Schett, Georg
中科院分区：
文献类型：
--
作者：
Diarra, Danielle;Stolina, Marina;Schett, Georg
退行性和炎症性关节疾病导致关节结构的破坏。退行性骨关节炎导致新骨的形成，而类风湿性关节炎导致骨吸收。这些不同类型关节疾病的分子基础尚不清楚。通过抑制Dickkopf-1（DKK-1），Wnt通路的调节分子，我们能够将类风湿性关节炎小鼠模型的骨破坏模式逆转为骨关节炎的骨形成模式。这样，虽然形成了骨结节，也就是所谓的骨赘，但并没有造成整体的骨质侵蚀。我们在小鼠炎症性关节炎模型和人类类风湿性关节炎中确定了肿瘤坏死因子-α（TNF）作为DKK-1的关键诱导剂。这些结果表明，Wnt通路是关节重塑的关键调节因子。
Degenerative and inflammatory joint diseases lead to a destruction of the joint architecture. Whereas degenerative osteoarthritis results in the formation of new bone, rheumatoid arthritis leads to bone resorption. The molecular basis of these different patterns of joint disease is unknown. By inhibiting Dickkopf-1 (DKK-1), a regulatory molecule of the Wnt pathway, we were able to reverse the bone-destructive pattern of a mouse model of rheumatoid arthritis to the bone-forming pattern of osteoarthritis. In this way, no overall bone erosion resulted, although bony nodules, so-called osteophytes, did form. We identified tumor necrosis factor-alpha (TNF) as a key inducer of DKK-1 in the mouse inflammatory arthritis model and in human rheumatoid arthritis. These results suggest that the Wnt pathway is a key regulator of joint remodeling.