Fibroblast growth factor receptor 1 regulates the differentiation and activation of osteoclasts through Erk1/2 pathway.
To elucidate the direct role and mechanism of FGFR1 signaling in the differentiation and activation of osteoclasts, we conditionally inactivated FGFR1 in bone marrow monocytes and mature osteoclasts of mice. Mice deficient in FGFR1 (Fgfr1(-/-)) exhibited misregulated bone remodeling with reduced osteoclast number and impaired osteoclast function. In vitro assay demonstrated that the number of tartrate-resistant acid phosphatase (TRAP) positive osteoclasts derived from bone marrow monocytes of Fgfr1(-/-) mice was significantly diminished. The bone resorption activity of mature osteoclasts derived from Fgfr1(-/-) mice was also suppressed. Further analysis showed that the osteoclasts with FGFR1 deficiency exhibited downregulated expression of genes related to osteoclastic activity including TRAP and MMP-9. The phosphorylation of Erk1/2 mitogen-activated protein (MAP) kinase was also decreased. Our results suggest that FGFR1 is indispensable for complete differentiation and activation of osteoclasts in mice.
Lu
Xiumin
X
State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Su
Nan
N
Yang
Jing
J
Huang
Wei
W
Li
Can
C
Zhao
Ling
L
He
Qifen
Q
Du
Xiaolan
X
Shen
Yue
Y
Chen
Bo
B
Chen
Lin
L
D000135:Acid Phosphatase / Q000737:chemistry; D000818:Animals; D002454:Cell Differentiation; D007527:Isoenzymes / Q000737:chemistry; D051379:Mice; D008817:Mice, Mutant Strains; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase
D007527:Isoenzymes; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase