کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1941728 1536903 2016 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The inhibitors of cyclin-dependent kinases and GSK-3β enhance osteoclastogenesis
ترجمه فارسی عنوان
مهارکننده های کیناز وابسته به سیکلین و GSK-3β باعث افزایش استئوکلستوژنز می شود
کلمات کلیدی
مهار کننده Cdks؛ مهار کننده GSK-3β؛ استئوکلاست
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
چکیده انگلیسی


• We performed a chemical genetic screen to identify drugs which modulate osteoclastogenesis.
• The screening determined a Cdk/GSK-3β inhibitor, kenpaullone, and two Cdk inhibitors, olomoucine and roscovitine, as activators of osteoclastogenesis.
• The kenpaullone, olomoucine, and roscovitine induce an enhanced osteoclastogenesis by upregulating NFATc1 and mature cathepsin K levels.

Osteoclasts are multinucleated cells with bone resorption activity that is crucial for bone remodeling. RANK‐RANKL (receptor activator of nuclear factor κB ligand) signaling has been shown as a main signal pathway for osteoclast differentiation. However, the molecular mechanism and the factors regulating osteoclastogenesis remain to be fully understood. In this study, we performed a chemical genetic screen, and identified a Cdks/GSK-3β (cyclin-dependent kinases/glycogen synthase kinase 3β) inhibitor, kenpaullone, and two Cdks inhibitors, olomoucine and roscovitine, all of which significantly enhance osteoclastogenesis of RAW264.7 cells by upregulating NFATc1 (nuclear factor of activated T cells, cytoplasmic 1) levels. We also determined that the all three compounds increase the number of osteoclast differentiated from murine bone marrow cells. Furthermore, the three inhibitors, especially kenpaullone, promoted maturation of cathepsin K, suggesting that the resorption activity of the resultant osteoclasts is also activated. Our findings indicate that inhibition of GSK-3β and/or Cdks enhance osteoclastogenesis by modulating the RANK–RANKL signaling pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemistry and Biophysics Reports - Volume 5, March 2016, Pages 253–258
نویسندگان
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