Gravallese E M, Manning C, Tsay A, Naito A, Pan C, Amento E, Goldring S R
Beth Israel Deaconess Medical Center, New England Baptist Bone and Joint Institute, and Harvard Medical School, Boston, Massachusetts, USA.
Arthritis Rheum. 2000 Feb;43(2):250-8. doi: 10.1002/1529-0131(200002)43:2<250::AID-ANR3>3.0.CO;2-P.
Osteoclast differentiation factor (ODF; also known as osteoprotegerin ligand, receptor activator of nuclear factor kappaB ligand, and tumor necrosis factor-related activation-induced cytokine) is a recently described cytokine known to be critical in inducing the differentiation of cells of the monocyte/macrophage lineage into osteoclasts. The role of osteoclasts in bone erosion in rheumatoid arthritis (RA) has been demonstrated, but the exact mechanisms involved in the formation and activation of osteoclasts in RA are not known. These studies address the potential role of ODF and the bone and marrow microenvironment in the pathogenesis of osteoclast-mediated bone erosion in RA.
Tissue sections from the bone-pannus interface at sites of bone erosion were examined for the presence of osteoclast precursors by the colocalization of messenger RNA (mRNA) for tartrate-resistant acid phosphatase (TRAP) and cathepsin K in mononuclear cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to identify mRNA for ODF in synovial tissues, adherent synovial fibroblasts, and activated T lymphocytes derived from patients with RA.
Multinucleated cells expressing both TRAP and cathepsin K mRNA were identified in bone resorption lacunae in areas of pannus invasion into bone in RA patients. In addition, mononuclear cells expressing both TRAP and cathepsin K mRNA (preosteoclasts) were identified in bone marrow in and adjacent to areas of pannus invasion in RA erosions. ODF mRNA was detected by RT-PCR in whole synovial tissues from patients with RA but not in normal synovial tissues. In addition, ODF mRNA was detected in cultured adherent synovial fibroblasts and in activated T lymphocytes derived from RA synovial tissue, which were expanded by exposure to anti-CD3.
TRAP-positive, cathepsin K-positive osteoclast precursor cells are identified in areas of pannus invasion into bone in RA. ODF is expressed by both synovial fibroblasts and by activated T lymphocytes derived from synovial tissues from patients with RA. These synovial cells may contribute directly to the expansion of osteoclast precursors and to the formation and activation of osteoclasts at sites of bone erosion in RA.
破骨细胞分化因子（ODF；也称为骨保护素配体、核因子κB受体激活剂和肿瘤坏死因子相关激活诱导细胞因子）是一种最近被描述的细胞因子，已知在诱导单核细胞/巨噬细胞谱系细胞分化为破骨细胞过程中起关键作用。破骨细胞在类风湿关节炎（RA）骨侵蚀中的作用已得到证实，但RA中破骨细胞形成和激活的确切机制尚不清楚。这些研究探讨了ODF以及骨和骨髓微环境在RA中破骨细胞介导的骨侵蚀发病机制中的潜在作用。
通过抗酒石酸酸性磷酸酶（TRAP）和组织蛋白酶K的信使核糖核酸（mRNA）在单核细胞中的共定位，检查骨侵蚀部位骨-血管翳界面的组织切片中破骨细胞前体的存在情况。采用逆转录聚合酶链反应（RT-PCR）鉴定RA患者滑膜组织、贴壁滑膜成纤维细胞和活化T淋巴细胞中ODF的mRNA。
在RA患者血管翳侵入骨区域的骨吸收陷窝中，鉴定出同时表达TRAP和组织蛋白酶K mRNA的多核细胞。此外，在RA侵蚀血管翳侵入区域内及相邻的骨髓中，鉴定出同时表达TRAP和组织蛋白酶K mRNA的单核细胞（前破骨细胞）。通过RT-PCR在RA患者的全滑膜组织中检测到ODF mRNA，但在正常滑膜组织中未检测到。此外，在培养的贴壁滑膜成纤维细胞和来自RA滑膜组织的活化T淋巴细胞中检测到ODF mRNA，这些细胞通过暴露于抗CD3而扩增。
在RA血管翳侵入骨的区域中，鉴定出TRAP阳性、组织蛋白酶K阳性的破骨细胞前体细胞。ODF由RA患者滑膜成纤维细胞和来自滑膜组织的活化T淋巴细胞表达。这些滑膜细胞可能直接促成破骨细胞前体的扩增以及RA骨侵蚀部位破骨细胞的形成和激活。
