GDNF secreted by pre-osteoclasts induces migration of bone marrow mesenchymal stem cells and stimulates osteogenesis
- 주제(키워드) Bone homeostasis , Bone marrow mesenchymal stem cell , Cell migration , Glial cell-derived neurotrophic factor , Osteogenesis
- 주제(기타) Biochemistry & Molecular Biology
- 설명문(일반) [Yi, Sol; Kim, Jihee; Lee, Soo Young] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Yi, Sol; Kim, Jihee; Lee, Soo Young] Ewha Womans Univ, Res Ctr Cellular Homeostasis, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- OA유형 Green Published, gold
- 발행기관 KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000175454
- 본문언어 영어
- Published As http://dx.doi.org/10.5483/BMBRep.2020.53.12.199
- PubMed https://pubmed.ncbi.nlm.nih.gov/33148376
초록/요약
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 marrow-derived 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 GFR alpha 1 complex. Overall, this study highlights the role of POC-derived GDNF in BMMSC migration and osteogenic differentiation, suggesting that GDNF regulates bone metabolism.
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