Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Ann Rheum Dis. 2010 Jan;69 Suppl 1:i83-85. doi: 10.1136/ard.2009.120188.
Analysis of tissues retrieved from the bone-pannus interface from patients with rheumatoid arthritis (RA) and studies in animal models of inflammatory arthritis provide strong evidence that osteoclasts, the cells that are essential for physiological bone resorption, are responsible for articular bone destruction in RA. However, current treatments that specifically target osteoclast-mediated bone resorption in RA have not been successful in preventing bone erosions, and new therapeutic strategies are needed. It has been noted that, although osteoclast precursors are present within the bone microenvironment at sites of pathological bone resorption, cells expressing the full morphological and functional properties of mature osteoclasts are restricted to the immediate bone surface and adjacent calcified cartilage. These findings provide evidence that, in addition to requirements for specific cytokines, interaction of osteoclast precursors with these mineralised matrices results in activation of specific signal pathways and the induction of unique gene products that are essential for terminal osteoclast differentiation and activation. These studies are designed to define the gene products and signalling pathways regulated by bone and calcified cartilage, to identify new molecular targets and novel therapeutic approaches for preventing osteoclast-mediated joint destruction in RA and related forms of pathological bone loss.
对类风湿关节炎 (RA) 患者的骨赘界面中取出的组织进行分析，并在炎症性关节炎的动物模型中进行研究，为破骨细胞是负责 RA 关节骨破坏的关键细胞提供了有力证据。然而，目前专门针对 RA 中破骨细胞介导的骨吸收的治疗方法并未成功预防骨侵蚀，需要新的治疗策略。已经注意到，尽管破骨细胞前体存在于病理性骨吸收部位的骨微环境中，但表达成熟破骨细胞完整形态和功能特性的细胞仅限于骨表面和相邻的钙化软骨。这些发现提供了证据表明，除了特定细胞因子的要求外，破骨细胞前体与这些矿化基质的相互作用导致特定信号通路的激活，并诱导独特的基因产物，这些基因产物对于终末破骨细胞分化和激活是必需的。这些研究旨在确定受骨和钙化软骨调节的基因产物和信号通路，以鉴定预防 RA 和相关病理性骨丢失中破骨细胞介导的关节破坏的新的分子靶点和新的治疗方法。
