Fibronectin Inhibits Osteoclastogenesis While Enhancing Osteoclast Activity via Nitric Oxide and Interleukin-1β-Mediated Signaling Pathways
Fibronectin Inhibits Osteoclastogenesis While Enhancing Osteoclast Activity via Nitric Oxide and Interleukin-1β-Mediated Signaling Pathways
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DOI：
10.1002/jcb.22791
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发表时间：
2010-11-01
影响因子：
4
通讯作者：
Manolson, Morris F.
中科院分区：
文献类型：
--
作者：
Gramoun, Azza;Azizi, Natoosha;Manolson, Morris F.
破骨细胞是由单核前体细胞融合形成的骨吸收细胞。基质蛋白、纤连蛋白 (FN)、玻连蛋白 (VN) 和骨桥蛋白 (OPN) 与关节破坏有关，并主要通过整合素与破骨细胞相互作用。为了评估这些基质蛋白对破骨细胞形成和活性的影响，我们在预先涂有 0.01-20 μg/ml FN、VN 和 OPN 的组织培养聚苯乙烯 (TCP) 或骨学 (TM) 载玻片上使用 RAW 264.7 (RAW) 细胞和分化为破骨细胞的小鼠脾细胞。 96 小时时，在 RAW 和脾细胞培养物中，与 OPN 和 TCP 相比，VN 和 FN 上的破骨细胞数量和多核细胞均减少。当评估早期分化时，VN而不是FN在48小时时降低细胞质抗酒石酸酸性磷酸酶活性和前破骨细胞数量。 OPN 对破骨细胞形成的影响与 FN 相反。当RAW细胞在OPN上分化并经FN和OPN处理时，仅FN处理组的破骨细胞数量比对照组低40-60%，而细胞核总数没有变化，表明EN延迟了破骨细胞融合。与其对破骨细胞生成的抑制作用相反，FN 通过增加破骨细胞活性和再吸收破骨细胞的百分比来增加吸收。伴随着一氧化氮 (NO) 和白细胞介素 1 β (IL-1 β) 水平的增加。使用 NO 合酶抑制剂仅对 FN 抑制 IL-1 β 的产生，表明 NO 和 IL-1 β 信号通路之间存在 FN 特异性串扰。我们得出的结论是，FN 尽管抑制破骨细胞形成，但仍上调破骨细胞活性，并且这些作用涉及 NO 和 IL-1 β 信号传导。 J.细胞。生物化学。 111: 1020-1034, 2010。(C) 2010 Wiley-Liss, Inc.
Osteoclasts are bone-resorbing cells formed by fusion of mononuclear precursors. The matrix proteins, fibronectin (FN), vitronectin (VN), and osteopontin (OPN) arc implicated in joint destruction and interact with osteoclasts mainly through integrins. To assess the effects of these matrix proteins on osteoclast formation and activity, we used RAW 264.7 (RAW) cells and mouse splenocytes differentiated into osteoclasts on tissue culture polystyrene (TCP) or osteologic (TM) slides pre-coated with 0.01-20 mu g/ml FN, VN, and OPN. At 96h, osteoclast number and multinucleation were decreased on VN and FN compared to OPN and TCP in both RAW and splenocytes cell cultures. When early differentiation was assessed, VN but not FN decreased cytoplasmic tartrate-resistant acid phosphatase activity and pre-osteoclast number at 48 h. OPN had the opposite effect to FN on osteoclast formation. When RAW cells were differentiated on OPN and treated by FN and OPN, osteoclast number only in the FN treated group was 40-60% lower than the control, while the total number of nuclei was unchanged, suggesting that EN delays osteoclast fusion. In contrast to its inhibitory effect on osteoclastogenesis, FN increased resorption by increasing both osteoclast activity and the percentage of resorbing osteoclasts. This was accompanied by an increase in nitric oxide (NO) levels and interleukin-1 beta (IL-1 beta). IL-1 beta production was inhibited using the NO-synthase inhibitor only on FN indicating a FN-specific cross-talk between NO and IL-1 beta signaling pathways. We conclude that FN upregulates osteoclast activity despite inhibiting osteoclast formation and that these effects involve NO and IL-1 beta signaling. J. Cell. Biochem. 111: 1020-1034, 2010. (C) 2010 Wiley-Liss, Inc.