Osteoblast Function Is Compromised at Sites of Focal Bone Erosion in Inflammatory Arthritis
Osteoblast Function Is Compromised at Sites of Focal Bone Erosion in Inflammatory Arthritis
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DOI：
10.1359/jbmr.090320
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发表时间：
2009-09-01
影响因子：
6.2
通讯作者：
Gravallese, Ellen M.
中科院分区：
文献类型：
--
作者：
Walsh, Nicole C.;Reinwald, Susan;Gravallese, Ellen M.
在类风湿关节炎(RA)中，滑膜炎症导致关节骨局灶性侵蚀。尽管治疗可以减轻炎症，但在RA患者中，侵蚀的修复和新骨的充分形成并不常见，这表明这些部位的骨形成可能受到影响。在RA小鼠模型中使用动态骨组织形态计量学来确定炎症对侵蚀的关节炎骨中的成骨细胞功能的影响。炎症附近骨表面的骨形成率与非关节炎骨中观察到的相似；因此，成骨细胞的活动不太可能补偿这些部位增加的骨吸收。在关节炎骨中，与正常骨髓相邻的骨面相比，炎症邻近的骨面的活跃矿化表面的范围较小。与矿化骨形成减少一致的是，尽管明显存在表达早期成骨细胞系标记Runx2的细胞，但表达中晚期成骨细胞系标记碱性磷酸酶的细胞明显稀少。此外，几个WRIT信号拮抗剂的Dickkopf和分泌型Frizzled相关蛋白家族成员在关节炎滑膜组织中表达上调，提示WRIT信号的抑制可能是导致关节炎骨内成骨细胞功能受损的机制之一。总之，这些数据表明，关节炎骨内炎症的存在损害了成骨细胞形成足够矿化骨的能力，从而导致RA局灶性骨侵蚀部位的骨净丢失和骨修复失败。《矿工杂志》2009；24：1572-1585。2009年3月30日在线发布；DOI：10.1359/JBMR.090320
In rheumatoid arthritis (RA), synovial inflammation results in focal erosion of articular bone. Despite treatment attenuating inflammation, repair of erosions with adequate formation of new bone is uncommon in RA, suggesting that bone formation may be compromised at these sites. Dynamic bone histomorphometry was used in a murine model of RA to determine the impact of inflammation on osteoblast function within eroded arthritic bone. Bone formation rates at bone surfaces adjacent to inflammation were similar to those observed in nonarthritic bone; therefore, osteoblast activity is unlikely to compensate for the increased bone resorption at these sites. Within arthritic bone, the extent of actively mineralizing surface was reduced at bone surfaces adjacent to inflammation compared with bone surfaces adjacent to normal marrow. Consistent with the reduction in mineralized bone formation, there was a notable paucity of cells expressing the mid- to late stage osteoblast lineage marker alkaline phosphatase, despite a clear presence of cells expressing the early osteoblast lineage marker Runx2. In addition, several members of the Dickkopf and secreted Frizzled-related protein families of Writ signaling antagonists were upregulated in arthritic synovial tissues, suggesting that inhibition of Writ signaling could be one mechanism contributing to impaired osteoblast function within arthritic bone. Together, these data indicate that the presence of inflammation within arthritic bone impairs osteoblast capacity to form adequate mineralized bone, thus contributing to the net loss of bone and failure of bone repair at sites of focal bone erosion in RA. J Bone Miner Res 2009;24:1572-1585. Published online on March 30, 2009; doi: 10.1359/JBMR.090320