ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2015
ERK1 and ERK2 regulate chondrocyte terminal differentiation during endochondral bone formation.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015. 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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40 citing papers in PubMed, 75 citations in OpenAlex.
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- IER3: exploring its dual function as an oncogene and tumor suppressor.Cancer gene therapy · 2025Article
- Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation.Bone · 2024Article
- Impaired fracture healing is associated with callus chondro-osseous junction abnormalities in periostin-null and osteopontin-null mice.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- Cell-based screen identifies porphyrins as FGFR3 activity inhibitors with therapeutic potential for achondroplasia and cancer.JCI insight · 2023Article
- Phosphate-induced activation of VEGFR2 leads to caspase-9-mediated apoptosis of hypertrophic chondrocytes.iScience · 2023Article
- Review
- Blocking circadian clock factor Rev-erbα inhibits growth plate chondrogenesis via up-regulating MAPK-ERK1/2 pathway.Cell cycle (Georgetown, Tex.) · 2023Article
- Comparative proteomic analysis identifies differentially expressed proteins and reveals potential mechanisms of traumatic heterotopic ossification progression.Journal of orthopaedic translation · 2022Article
- 4PBA reduces growth deficiency in osteogenesis imperfecta by enhancing transition of hypertrophic chondrocytes to osteoblasts.JCI insight · 2022Article
- NG2/CSPG4 regulates cartilage degeneration during TMJ osteoarthritis.Frontiers in dental medicine · 2022Article
- Protective effect of adrenomedullin on hyperoxia-induced lung injury.Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2021Article
- Targeting chondrocytes for arresting bony fusion in ankylosing spondylitis.Nature communications · 2021Article
- SPRY4 acts as an indicator of osteoarthritis severity and regulates chondrocyte hypertrophy and ECM protease expression.NPJ Regenerative medicine · 2021Article
- Enhancing the potential of aged human articular chondrocytes for high-quality cartilage regeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Enchondromatosis and Growth Plate Development.Current osteoporosis reports · 2021Review
- A Comprehensive Analysis of SE-lncRNA/mRNA Differential Expression Profiles During Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.Frontiers in cell and developmental biology · 2021Article
- An ECHO of Cartilage:Frontiers in bioengineering and biotechnology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Chondrocytes in the epiphyseal cartilage undergo terminal differentiation prior to their removal through apoptosis. To examine the role of ERK1 and ERK2 in chondrocyte terminal differentiation, we generated Osterix (Osx)-Cre; ERK1(-/-) ; ERK2(flox/flox) mice (conditional knockout Osx [cKOosx]), in which ERK1 and ERK2 were deleted in hypertrophic chondrocytes. These cKOosx mice were grossly normal in size at birth, but by 3 weeks of age exhibited shorter long bones. Histological analysis in these mice revealed that the zone of hypertrophic chondrocytes in the growth plate was markedly expanded. In situ hybridization and quantitative real-time PCR analyses demonstrated that Matrix metalloproteinase-13 (Mmp13) and Osteopontin expression was significantly decreased, indicating impaired chondrocyte terminal differentiation. Moreover, Egr1 and Egr2, transcription factors whose expression is restricted to the last layers of hypertrophic chondrocytes in wild-type mice, were also strongly downregulated in these cKOosx mice. In transient transfection experiments in the RCS rat chondrosarcoma cell line, the expression of Egr1, Egr2, or a constitutively active mutant of MEK1 increased the activity of an Osteopontin promoter, whereas the MEK1-induced activation of the Osteopontin promoter was inhibited by the coexpression of Nab2, an Egr1 and Egr2 co-repressor. These results suggest that MEK1-ERK signaling activates the Osteopontin promoter in part through Egr1 and Egr2. Finally, our histological analysis of cKOosx mice demonstrated enchondroma-like lesions in the bone marrow that are reminiscent of human metachondromatosis, a skeletal disorder caused by mutations in PTPN11. Our observations suggest that the development of enchondromas in metachondromatosis may be caused by reduced extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK MAPK) signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.