Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis.
Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis.
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发表时间：
1998-04
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通讯作者：
E. Gravallese;Y. Harada;Jeng-Tzang Wang;A. Gorn;T. Thornhill;S. Goldring
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作者：
E. Gravallese;Y. Harada;Jeng-Tzang Wang;A. Gorn;T. Thornhill;S. Goldring
骨-血管翳界面的局灶性骨吸收在类风湿性关节炎（RA）和幼年型类风湿性关节炎（JRA）中很常见，可导致显著的发病率。然而，参与这一过程的特定细胞和激素机制尚未完全确立。我们检查了RA和JRA患者骨侵蚀区域的组织切片。如前所述，多核细胞（MNC）存在于钙化软骨区域的吸收陷窝和紧邻钙化软骨的软骨下骨中。降钙素受体（CTR）的mRNA定位于骨吸收陷窝中的这些MNC，这一发现明确将这些细胞鉴定为破骨细胞。这些MNCs抗酒石酸酸性磷酸酶（TRAP）mRNA和TRAP酶活性也呈阳性。骨表面上偶尔的单核细胞也呈CTR阳性。未在骨表面的单核细胞和MNCs为CTR阴性。CTR阳性细胞局限于矿化组织表面表明，骨和/或钙化软骨提供了造血破骨细胞前体分化为完全分化的破骨细胞的关键信号。骨外和浸润组织中的一些MNC和单核细胞呈TRAP阳性。这些细胞可能代表骨上CTR-TRAP阳性细胞的前体。甲状旁腺激素受体mRNA存在于成骨细胞表型外观的细胞中，靠近MNC，偶尔在血管翳组织内的细胞中，但在骨吸收陷窝的MNC中不存在。这些发现表明，类风湿病变中的破骨细胞不表达甲状旁腺激素受体。总之，RA中的再吸收细胞表现出明确的破骨细胞表型，这表明抑制破骨细胞募集或活性的药理学药物是RA和JRA患者阻断局灶性骨侵蚀的合理靶点。
Focal resorption of bone at the bone-pannus interface is common in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and can result in significant morbidity. However, the specific cellular and hormonal mechanisms involved in this process are not well established. We examined tissue sections from areas of bone erosion in patients with RA and JRA. Multinucleated cells (MNCs) were present in resorption lacunae in areas of calcified cartilage and in subchondral bone immediately adjacent to calcified cartilage, as previously described. mRNA for the calcitonin receptor (CTR) was localized to these MNCs in bone resorption lacunae, a finding that definitively identifies these cells as osteoclasts. These MNCs were also positive for tartrate-resistant acid phosphatase (TRAP) mRNA and TRAP enzymatic activity. Occasional mononuclear cells on the bone surface were also CTR positive. Mononuclear cells and MNCs not on bone surfaces were CTR negative. The restriction of CTR-positive cells to the surface of mineralized tissues suggests that bone and/or calcified cartilage provide signals that are critical for the differentiation of hematopoietic osteoclast precursors to fully differentiated osteoclasts. Some MNCs and mononuclear cells off bone and within invading tissues were TRAP positive. These cells likely represent the precursors of the CTR-TRAP-positive cells on bone. Parathyroid hormone receptor mRNA was present in cells with the phenotypic appearance of osteoblasts, in close proximity to MNCs, and in occasional cells within pannus tissue, but not in the MNCs in bone resorption lacunae. These findings demonstrate that osteoclasts within the rheumatoid lesion do not express parathyroid hormone receptor. In conclusion, the resorbing cells in RA exhibit a definitive osteoclastic phenotype, suggesting that pharmacological agents that inhibit osteoclast recruitment or activity are rational targets for blocking focal bone erosion in patients with RA and JRA.