ArticleJournal of bone and mineral metabolism2012
FGF and ERK signaling coordinately regulate mineralization-related genes and play essential roles in osteocyte differentiation.
Article in Journal of bone and mineral metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 67 citations in OpenAlex.
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- Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis.Journal of anatomy · 2024Article
- MEK-inhibitors decrease Nfix in muscular dystrophy but induce unexpected calcifications, partially rescued with Cyanidin diet.iScience · 2024Article
- Distinct role of Klotho in long bone and craniofacial bone: skeletal development, repair and regeneration.PeerJ · 2024Review
- Modulation of the pre-metastatic bone niche: molecular changes mediated by bone-homing prostate cancer extracellular vesicles.Frontiers in cell and developmental biology · 2024Article
- Extracellular FeScientific reports · 2023Article
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- Contributions of Resin Cast Etching to Visualising the Osteocyte Lacuno-Canalicular Network Architecture in Bone Biology and Tissue Engineering.Calcified tissue international · 2023Review
- Development of Erf-Mediated Craniosynostosis and Pharmacological Amelioration.International journal of molecular sciences · 2023Article
- The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- An optimized cocktail of small molecule inhibitors promotes the maturation of dendritic cells in GM-CSF mouse bone marrow culture.Frontiers in immunology · 2023Article
- Pathways Controlling Formation and Maintenance of the Osteocyte Dendrite Network.Current osteoporosis reports · 2022Review
- Protein tyrosine phosphatases in skeletal development and diseases.Bone research · 2022Review
- Osteoblast Dysfunction in Non-Hereditary Sclerosing Bone Diseases.International journal of molecular sciences · 2021Review
- Erf Affects Commitment and Differentiation of Osteoprogenitor Cells in Cranial Sutures via the Retinoic Acid Pathway.Molecular and cellular biology · 2021Article
- Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice.Frontiers in cell and developmental biology · 2021Article
- Article
- Fibroblast growth factors signaling in bone metastasis.Endocrine-related cancer · 2020Review
- A Novel 3D Osteoblast and Osteocyte Model Revealing Changes in Mineralization and Pro-osteoclastogenic Paracrine Signaling During Estrogen Deficiency.Frontiers in bioengineering and biotechnology · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
To examine the roles of FGF and ERK MAPK signaling in osteocyte differentiation and function, we performed microarray analyses using the osteocyte cell line MLO-Y4. This experiment identified a number of mineralization-related genes that were regulated by FGF2 in an ERK MAPK-dependent manner. Real-time PCR analysis indicated that FGF2 upregulates Ank, Enpp1, Mgp, Slc20a1, and Dmp1 in MLO-Y4 cells. Consistent with this observation, the selective FGF receptor inhibitor PD173074 decreased Ank, Enpp1, Slc20a1, and Dmp1 mRNA expression in mouse calvaria in organ culture. Since Dmp1 plays a central role in osteocyte differentiation and mineral homeostasis, we further analyzed FGF regulation of Dmp1. Similar to FGF2, FGF23 upregulated Dmp1 expression in MLO-Y4 cells in the presence of Klotho. Furthermore, increased extracellular phosphate levels partially inhibited FGF2-induced upregulation of Dmp1 mRNA expression, suggesting a coordinated regulation of Dmp1 expression by FGF signaling and extracellular phosphate. In MLO-Y4 osteocytes and in MC3T3E1 and primary calvaria osteoblasts, U0126 strongly inhibited both basal expression of Dmp1 mRNA and FGF2-induced upregulation. Consistent with the in vitro observations, real-time PCR and immunohistochemical analysis showed a strong decrease in Dmp1 expression in the skeletal elements of ERK1(-/-); ERK2(flox/flox); Prx1-Cre mice. Furthermore, scanning electron microscopic analysis revealed that no osteocytes with characteristic dendritic processes develop in the limbs of ERK1(-/-); ERK2 (flox/flox); Prx1-Cre mice. Collectively, our observations indicate that FGF signaling coordinately regulates mineralization-related genes in the osteoblast lineage and that ERK signaling is essential for Dmp1 expression and osteocyte differentiation.
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