TY - JOUR
T1 - GDNF secreted by pre-osteoclasts induces migration of bone marrow mesenchymal stem cells and stimulates osteogenesis
AU - Yi, Sol
AU - Kim, Jihee
AU - Lee, Soo Young
N1 - Funding Information:
This work was supported by grants from the National Research Foundation of Korea (2019R1A5A6099645; 2019R1A6C1010020) and by the Ewha Womans University Research Grant (1-2017-1157-001).
Publisher Copyright:
© 2020. the The Korean Society for Biochemistry and Molecular Biology. All Rights Reserved.
PY - 2020
Y1 - 2020
N2 - 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 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]
AB - 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 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]
KW - Bone homeostasis
KW - Bone marrow mesenchymal stem cell
KW - Cell migration
KW - Glial cell-derived neurotrophic factor
KW - Osteogenesis
UR - http://www.scopus.com/inward/record.url?scp=85099171462&partnerID=8YFLogxK
U2 - 10.5483/BMBRep.2020.53.12.199
DO - 10.5483/BMBRep.2020.53.12.199
M3 - Article
C2 - 33148376
AN - SCOPUS:85099171462
SN - 1976-6696
VL - 53
SP - 646
EP - 651
JO - BMB Reports
JF - BMB Reports
IS - 12
ER -