کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8624950 | 1568109 | 2018 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Secreted Clusterin protein inhibits osteoblast differentiation of bone marrow mesenchymal stem cells by suppressing ERK1/2 signaling pathway
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کلمات کلیدی
OCNPPARγ2distal-less homeobox 5C/EBP-αDlx5COL1A1LPLAPM1OPNAP2Msx2RUNX2BMSCsSCLUCCAAT/enhancer-binding protein alpha - CCAAT / پروتئین آلفا اتصال دهنده تقویت کنندهAdipocyte - آدیپوسیتadiponectin - آدیپونکتینALP - آلکالن فسفاتازAlkaline phosphatase - آلکالین فسفاتاز یا فسفاتاز قلیاییOsteoblast - استئوبلاست Osteopontin - استئوپنتینOsteocalcin - استئوکلسین Osteoblast differentiation - تمایز استئوبلاستclusterin - خوسترینMesenchymal stem cells - سلول های بنیادی مزانشیمیRunt-related transcription factor 2 - عامل رونویسی مرتبط با روت 2Lipoprotein lipase - لیپو پروتئین لیپازCollagen type 1 - نوع کلاژن 1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
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چکیده انگلیسی
Secreted Clusterin (sCLU, also known as Apolipoprotein J) is an anti-apoptotic glycoprotein involved in the regulation of cell proliferation, lipid transport, extracellular tissue remodeling and apoptosis. sCLU is expressed and secreted by mouse bone marrow-derived skeletal (stromal or mesenchymal) stem cells (mBMSCs), but its functional role in MSC biology is not known. In this study, we demonstrated that Clusterin mRNA expression and protein secretion in conditioned medium increased during adipocyte differentiation and decreased during osteoblast differentiation of mBMSCs. Treatment of mBMSC cultures with recombinant sCLU protein increased cell proliferation and exerted an inhibitory effect on the osteoblast differentiation while stimulated adipocyte differentiation in a dose-dependent manner. siRNA-mediated silencing of Clu expression in mBMSCs reduced adipocyte differentiation and stimulated osteoblast differentiation of mBMSCs. Furthermore, the inhibitory effect of sCLU on the osteoblast differentiation of mBMSCs was mediated by the suppression of extracellular signal-regulated kinase (ERK1/2) phosphorylation. In conclusion, we identified sCLU as a regulator of mBMSCs lineage commitment to osteoblasts versus adipocytes through a mechanism mediated by ERK1/2 signaling. Inhibiting sCLU is a possible therapeutic approach for enhancing osteoblast differentiation and consequently bone formation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 110, May 2018, Pages 221-229
Journal: Bone - Volume 110, May 2018, Pages 221-229
نویسندگان
Basem M. Abdallah, Abdullah M. Alzahrani, Moustapha Kassem,