Genetic inactivation of ERK1 and ERK2 in chondrocytes promotes bone growth and enlarges the spinal canal
| Autor: | Shunichi Murakami, Arjun S. Sebastian, Aya Kawanami, Takehiko Matsushita, Gary E. Landreth, Susan Mackem |
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| Rok vydání: | 2010 |
| Předmět: |
musculoskeletal diseases
MAPK/ERK pathway congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Thanatophoric dysplasia MAP Kinase Signaling System Synchondrosis Dwarfism Biology Article Gene Expression Regulation Enzymologic Achondroplasia Mice Chondrocytes Internal medicine medicine Animals Humans Orthopedics and Sports Medicine Spinal canal Mitogen-Activated Protein Kinase 1 Bone growth Foramen magnum Bone Development Mitogen-Activated Protein Kinase 3 Tibia Gene Expression Regulation Developmental musculoskeletal system medicine.disease Mice Mutant Strains Spine Cell biology Disease Models Animal medicine.anatomical_structure Endocrinology Spinal Canal |
| Zdroj: | Journal of Orthopaedic Research. 29:375-379 |
| ISSN: | 0736-0266 |
| DOI: | 10.1002/jor.21262 |
| Popis: | Activating mutations in FGFR3 cause the most common forms of human dwarfism: achondroplasia and thanatophoric dysplasia. In mouse models of achondroplasia, recent studies have implicated the ERK MAPK pathway, a pathway activated by FGFR3, in creating reduced bone growth. Our recent studies have indicated that increased Fgfr3 and ERK MAPK signaling in chondrocytes also causes premature synchondrosis closure in the cranial base and vertebrae, accounting for the sometimes fatal stenosis of the foramen magnum and spinal canal in achondroplasia. Conversely, whether the decrease--or inactivation--of ERK1 and ERK2 promotes bone growth and delays synchondrosis closure remains to be investigated. In this study, we inactivated ERK2 in the chondrocytes of ERK1-null mice using the Col2a1-Cre and Col2a1-CreER transgenes. We found that the genetic inactivation of ERK1 and ERK2 in chondrocytes enhances the growth of cartilaginous skeletal elements. We also found that the postnatal inactivation of ERK1 and ERK2 in chondrocytes delays synchondrosis closure and enlarges the spinal canal. These observations make ERK1 and ERK2 an attractive target for the treatment of achondroplasia and other FGFR3-related skeletal syndromes. |
| Databáze: | OpenAIRE |
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