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破骨细胞前体细胞分泌的 GDNF 诱导骨髓间充质干细胞迁移,并刺激成骨作用。

GDNF secreted by pre-osteoclasts induces migration of bone marrow mesenchymal stem cells and stimulates osteogenesis.

机构信息

Department of Life Science, Ewha Womans University, Seoul 03760; The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, Korea.

出版信息

BMB Rep. 2020 Dec;53(12):646-651. doi: 10.5483/BMBRep.2020.53.12.199.

DOI:10.5483/BMBRep.2020.53.12.199
PMID:33148376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7781916/
Abstract

Bone resorption is linked to bone formation via temporal and spatial coupling within the remodeling cycle. Several lines of evidence point to the critical role of coupling factors derived from pre-osteoclasts (POCs) during the regulation of bone marrowderived mesenchymal stem cells (BMMSCs). However, the role of glial cell-derived neurotrophic factor (GDNF) in BMMSCs is not completely understood. Herein, we demonstrate the role of POC-derived GDNF in regulating the migration and osteogenic differentiation of BMMSCs. RNA sequencing revealed GDNF upregulation in POCs compared with monocytes/macrophages. Specifically, BMMSC migration was inhibited by a neutralizing antibody against GDNF in pre-osteoclast-conditioned medium (POC-CM), whereas treatment with a recombinant GDNF enhanced migration and osteogenic differentiation. In addition, POC-CM derived from GDNF knock-downed bone marrow macrophages suppressed BMMSC migration and osteogenic differentiation. SPP86, a small molecule inhibitor, inhibits BMMSC migration and osteogenic differentiation by targeting the receptor tyrosine kinase RET, which is recruited by GDNF into the GFRα1 complex. Overall, this study highlights the role of POC-derived GDNF in BMMSC migration and osteogenic differentiation, suggesting that GDNF regulates bone metabolism. [BMB Reports 2020; 53(12): 646-651].

摘要

骨吸收通过重塑周期内的时间和空间偶联与骨形成相关联。有几条证据表明,来自破骨前体细胞(POC)的偶联因子在调节骨髓间充质干细胞(BMMSCs)中起着关键作用。然而,胶质细胞衍生的神经营养因子(GDNF)在 BMMSCs 中的作用尚不完全清楚。本文中,我们展示了 POC 衍生的 GDNF 在调节 BMMSCs 迁移和成骨分化中的作用。RNA 测序显示,与单核细胞/巨噬细胞相比,POC 中的 GDNF 上调。具体而言,在破骨前体细胞条件培养基(POC-CM)中,针对 GDNF 的中和抗体抑制了 BMMSC 的迁移,而重组 GDNF 的处理则增强了迁移和成骨分化。此外,源自 GDNF 敲低的骨髓巨噬细胞的 POC-CM 抑制了 BMMSC 的迁移和成骨分化。小分子抑制剂 SPP86 通过靶向 GDNF 招募到 GFRα1 复合物中的受体酪氨酸激酶 RET,从而抑制 BMMSC 的迁移和成骨分化。总的来说,这项研究强调了 POC 衍生的 GDNF 在 BMMSC 迁移和成骨分化中的作用,表明 GDNF 调节骨代谢。[BMB 报告 2020;53(12): 646-651]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7d5/7781916/d656f880d716/BMB-53-646-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7d5/7781916/1ffbf755fcd2/BMB-53-646-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7d5/7781916/24c25e3b94bf/BMB-53-646-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7d5/7781916/0fbb5de0989a/BMB-53-646-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7d5/7781916/d656f880d716/BMB-53-646-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7d5/7781916/1ffbf755fcd2/BMB-53-646-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7d5/7781916/24c25e3b94bf/BMB-53-646-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7d5/7781916/0fbb5de0989a/BMB-53-646-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7d5/7781916/d656f880d716/BMB-53-646-f4.jpg

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