Extracellular signal-regulated kinase 1 (ERK1) and ERK2 play essential roles in osteoblast differentiation and in supporting osteoclastogenesis.
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.
Matsushita
Takehiko
T
Department of Orthopaedics, Case Western Reserve University, 2109 Adelbert Road, BRB 329, Cleveland, OH 44106, USA.
Chan
Yuk Yu
YY
Kawanami
Aya
A
Balmes
Gener
G
Landreth
Gary E
GE
Murakami
Shunichi
S
D000818:Animals; D020029:Base Pairing / Q000235:genetics; D001842:Bone and Bones / Q000002:abnormalities / Q000201:enzymology; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology; D020219:Chondrogenesis; D002828:Choristoma / Q000150:complications / Q000201:enzymology; D004789:Enzyme Activation; D006132:Growth Plate / Q000166:cytology / Q000201:enzymology; D018398:Homeodomain Proteins / Q000235:genetics; D017880:Limb Deformities, Congenital / Q000150:complications / Q000201:enzymology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000172:deficiency / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000172:deficiency / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology* / Q000201:enzymology*; D010009:Osteochondrodysplasias / Q000150:complications / Q000201:enzymology; D010010:Osteoclasts / Q000166:cytology / Q000201:enzymology*; D010012:Osteogenesis; D011401:Promoter Regions, Genetic / Q000235:genetics; D053245:RANK Ligand / Q000378:metabolism
D018398:Homeodomain Proteins; C489936:Prrx1 protein, mouse; D053245:RANK Ligand; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse