Inflammatory microcrystals alter the functional phenotype of human osteoblast-like cells in vitro:: Synergism with IL-1 to overexpress cyclooxygenase-2
Inflammatory microcrystals alter the functional phenotype of human osteoblast-like cells in vitro:: Synergism with IL-1 to overexpress cyclooxygenase-2
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DOI：
10.4049/jimmunol.168.10.5310
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发表时间：
2002-05-15
影响因子：
4.4
通讯作者：
Poubelle, PE
中科院分区：
文献类型：
--
作者：
Bouchard, L;de Médicis, R;Poubelle, PE
慢性晶体相关性关节病，如痛风和假性痛风，可导致局部骨破坏。由于成骨细胞，通过可溶性因子和细胞与细胞的相互作用协调骨重塑，已被描述为与微晶接触，特别是在痛风的尿酸病灶，我们假设，微晶体的一水磷酸钙（MSUM）和焦磷酸钙二水合物（CPPD）可以改变成骨细胞的功能。扫描电镜显示，MSUM和CPPD在体外与人成骨细胞（hOB）粘附，并被部分吞噬。通过酶免疫测定法评估，MSUM和CPPD剂量依赖性刺激hOB中PGE（2）的产生，在IL-1存在下，这种反应协同增强。这种协同作用的机制是，至少部分地，在环氧化酶-2的表达水平，通过免疫印迹分析评估。MSUM和CPPD还刺激hOB中IL-6和IL-8的表达，并降低1，25-二羟维生素D-3诱导的碱性磷酸酶和骨钙素的活性（与IL-1无协同作用）。MSUM-或CPPD-刺激的IL-6的表达在hOB预处理与选择性环氧合酶-2抑制剂NS-398增加，不像单独诱导的IL-1，这是部分减少。用NS-398预处理hOB，MSUM-、CPPD-或IL-1-诱导的IL-8表达不变。这些结果表明，炎症性微晶改变了hOB的正常表型，将其重定向到骨形成减少和成骨细胞介导的骨吸收放大，这些异常可能在与慢性晶体诱导性关节炎相关的骨破坏中发挥作用。
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 micro-crystals, 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-dependent 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.