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Extracellular signal-regulated kinase 1 (ERK1) and ERK2 play essential roles in osteoblast differentiation and in supporting osteoclastogenesis.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2009 Nov; Vol. 29 (21), pp. 5843-57. Date of Electronic Publication: 2009 Sep 08. - Publication Year :
- 2009
-
Abstract
- Osteoblasts and chondrocytes arise from common osteo-chondroprogenitor cells. We show here that inactivation of ERK1 and ERK2 in osteo-chondroprogenitor cells causes a block in osteoblast differentiation and leads to ectopic chondrogenic differentiation in the bone-forming region in the perichondrium. Furthermore, increased mitogen-activated protein kinase signaling in mesenchymal cells enhances osteoblast differentiation and inhibits chondrocyte differentiation. These observations indicate that extracellular signal-regulated kinase 1 (ERK1) and ERK2 play essential roles in the lineage specification of mesenchymal cells. The inactivation of ERK1 and ERK2 resulted in reduced beta-catenin expression, suggesting a role for canonical Wnt signaling in ERK1 and ERK2 regulation of skeletal lineage specification. Furthermore, inactivation of ERK1 and ERK2 significantly reduced RANKL expression, accounting for a delay in osteoclast formation. Thus, our results indicate that ERK1 and ERK2 not only play essential roles in the lineage specification of osteo-chondroprogenitor cells but also support osteoclast formation in vivo.
- Subjects :
- Animals
Base Pairing genetics
Bone and Bones abnormalities
Bone and Bones enzymology
Chondrocytes cytology
Chondrocytes enzymology
Chondrogenesis
Choristoma complications
Choristoma enzymology
Enzyme Activation
Growth Plate cytology
Growth Plate enzymology
Homeodomain Proteins genetics
Limb Deformities, Congenital complications
Limb Deformities, Congenital enzymology
MAP Kinase Kinase 1 metabolism
Mesoderm cytology
Mesoderm enzymology
Mice
Mice, Knockout
Mitogen-Activated Protein Kinase 1 deficiency
Mitogen-Activated Protein Kinase 3 deficiency
Mutation genetics
Osteochondrodysplasias complications
Osteochondrodysplasias enzymology
Osteoclasts cytology
Promoter Regions, Genetic genetics
RANK Ligand metabolism
Cell Differentiation
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Osteoblasts cytology
Osteoblasts enzymology
Osteoclasts enzymology
Osteogenesis
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 29
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 19737917
- Full Text :
- https://doi.org/10.1128/MCB.01549-08