Bouchard Line, de Médicis Rinaldo, Lussier André, Naccache Paul H, Poubelle Patrice E
Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Pavillon Centre Hospitalier de l'Université Laval, Department of Medicine, Université Laval, 2705 Boulevard Laurier, Ste-Foy, Québec, Canada G1V 4G2.
J Immunol. 2002 May 15;168(10):5310-7. doi: 10.4049/jimmunol.168.10.5310.
Chronic crystal-associated arthropathies such as gout and pseudogout can lead to local bone destruction. Because osteoblasts, which orchestrate bone remodeling via soluble factors and cell-to-cell interactions, have been described in contact with microcrystals, particularly in uratic foci of gout, we hypothesized that microcrystals of monosodium urate monohydrate (MSUM) and of calcium pyrophosphate dihydrate (CPPD) could alter osteoblastic functions. MSUM and CPPD adhered to human osteoblastic cells (hOB) in vitro and were partly phagocytized as shown by scanning electron microscopy. MSUM and CPPD dose-dependently stimulated the production of PGE(2) in hOB as assessed by enzyme immunoassay, a response that was synergistically enhanced in the presence of IL-1. The mechanism of this synergism was, at least in part, at the level of the expression of cyclooxygenase-2 as evaluated by immunoblot analysis. MSUM and CPPD also stimulated the expression of IL-6 and IL-8 and reduced the 1,25-dihydroxyvitamin D(3)-induced activity of alkaline phosphatase and osteocalcin in hOB (with no synergism with IL-1). MSUM- or CPPD-stimulated expression of IL-6 in hOB pretreated with the selective cyclooxygenase-2 inhibitor NS-398 was increased, unlike that induced by IL-1 alone which was partially reduced. MSUM-, CPPD- or IL-1-induced expression of IL-8 was unchanged by pretreating hOB with NS-398. These results suggest that inflammatory microcrystals alter the normal phenotype of hOB, redirecting them toward reduced bone formation and amplified osteoblast-mediated bone resorption, abnormalities that could play a role in the bone destruction associated with chronic crystal-induced arthritis.
痛风和假性痛风等慢性晶体相关性关节病可导致局部骨质破坏。由于成骨细胞可通过可溶性因子和细胞间相互作用来协调骨重塑，且已有人描述成骨细胞与微晶接触，尤其是在痛风的尿酸盐病灶中，因此我们推测，一水合尿酸钠（MSUM）和二水焦磷酸钙（CPPD）的微晶可能会改变成骨细胞的功能。如扫描电子显微镜所示，MSUM和CPPD在体外可黏附于人成骨细胞（hOB），并部分被吞噬。通过酶免疫测定评估发现，MSUM和CPPD可剂量依赖性地刺激hOB中前列腺素E2（PGE(2)）的产生，在白细胞介素-1（IL-1）存在时，这种反应会协同增强。通过免疫印迹分析评估发现，这种协同作用的机制至少部分是在环氧合酶-2的表达水平上。MSUM和CPPD还刺激了IL-6和IL-8的表达，并降低了1,25-二羟基维生素D(3)诱导的hOB中碱性磷酸酶和骨钙素的活性（与IL-1无协同作用）。在用选择性环氧合酶-2抑制剂NS-398预处理的hOB中，MSUM或CPPD刺激的IL-6表达增加，这与单独IL-1诱导的情况不同，单独IL-1诱导的IL-6表达会部分降低。用NS-398预处理hOB后，MSUM、CPPD或IL-1诱导的IL-8表达没有变化。这些结果表明，炎性微晶会改变hOB的正常表型，使其转向骨形成减少和放大的成骨细胞介导的骨吸收，这些异常可能在与慢性晶体诱导的关节炎相关的骨质破坏中起作用。
