کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2553605 1560745 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The phosphatidylinositol 3-kinase-mediated production of interferon-β is critical for the lipopolysaccharide inhibition of osteoclastogenesis
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
The phosphatidylinositol 3-kinase-mediated production of interferon-β is critical for the lipopolysaccharide inhibition of osteoclastogenesis
چکیده انگلیسی

AimsThis study was performed to define molecular mechanisms underlying lipopolysaccharide (LPS)-induced inhibition of osteoclastogenesis.Main methodsThe LPS-dependent signaling pathways leading to the inhibition of osteoclastogenesis were examined using chemical inhibitors and neutralizing antibodies. Key findings: Lipopolysaccharide (LPS) has been shown to induce massive bone loss in vivo by stimulating osteoclast differentiation and activity. However, the direct effect of LPS on osteoclastogenesis in vitro is complex. Based on the context of the differentiation state of precursors, LPS has been shown to either augment or inhibit osteoclast differentiation. When added to receptor activator of NF-κB ligand (RANKL)-primed precursors, LPS enhances osteoclast differentiation via the production of TNF-α. On the other hand, LPS inhibits osteoclastogenesis from early precursors like bone marrow macrophages by hitherto unknown mechanism. In the present study, we investigated the mechanism by which LPS inhibits osteoclastogenesis. We have identified that the phosphatidylinositol 3-kinase (PI 3-kinase) dependent production of IFN-β and resultant inhibition of c-Fos expression upon LPS stimulation of bone marrow macrophages are responsible for the LPS-induced inhibition of osteoclastogenesis. Inhibition of PI 3-kinase, neutralization of IFN-β, and overexpression of c-Fos respectively prevented the LPS-induced inhibition of osteoclast differentiation.SignificanceOur results provide a molecular understanding of the differentiation stage-specific dual effect of LPS on osteoclastogenesis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 83, Issues 9–10, 29 August 2008, Pages 369–376
نویسندگان
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