BMP7 increases protein synthesis in SW1353 cells and determines rRNA levels in a NKX3-2-dependent manner
| Autor: | Ellen G. J. Ripmeester, Tim J. M. Welting, Guus G. H. van den Akker, Don A. M. Surtel, Jessica S. J. Steijns, Andy Cremers, Lodewijk W. van Rhijn, Marjolein M. J. Caron |
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| Přispěvatelé: | Orthopedie, RS: CAPHRI - R3 - Functioning, Participating and Rehabilitation, MUMC+: MA Orthopedie (9), RS: CAPHRI School for Public Health and Primary Care, MUMC+: MA Orthopedie (3) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Transcription
Genetic Bone Morphogenetic Protein 7 Up-Regulation/drug effects Core Binding Factor Alpha 1 Subunit urologic and male genital diseases Transcription Genetic/drug effects Cell Proliferation/drug effects POLYMERASE-I TRANSCRIPTION Ribosomal/genetics ACTS Promoter Regions Genetic PHOSPHORYLATION Cells Cultured Multidisciplinary Cultured Homeodomain Proteins/physiology Up-Regulation Chondrocytes/drug effects Chondrogenesis/drug effects embryonic structures Medicine Chondrogenesis Transcription Protein Biosynthesis/drug effects EXPRESSION animal structures Science Cells RUNX2 Transcription Factors/physiology Core Binding Factor Alpha 1 Subunit/genetics Promoter Regions Chondrocytes UBF Humans ARTICULAR CHONDROCYTES Promoter Regions Genetic/drug effects Cell Proliferation Homeodomain Proteins Genetic/drug effects GENE-TRANSCRIPTION urogenital system REPRESSION DNA RNA Ribosomal/genetics Bone Morphogenetic Protein 7/pharmacology RNA Ribosomal Protein Biosynthesis RNA Transcription Factors |
| Zdroj: | PLOS ONE, 17(2):e0263430. Public Library of Science PLoS ONE, Vol 17, Iss 2 (2022) |
| ISSN: | 1932-6203 |
| Popis: | BMP7 is a morphogen capable of counteracting the OA chondrocyte hypertrophic phenotype via NKX3-2. NKX3-2 represses expression of RUNX2, an important transcription factor for chondrocyte hypertrophy. Since RUNX2 has previously been described as an inhibitor for 47S pre-rRNA transcription, we hypothesized that BMP7 positively influences 47S pre-rRNA transcription through NKX3-2, resulting in increased protein translational capacity. Therefor SW1353 cells and human primary chondrocytes were exposed to BMP7 and rRNA (18S, 5.8S, 28S) expression was determined by RT-qPCR. NKX3-2 knockdown was achieved via transfection of a NKX3-2-specific siRNA duplex. Translational capacity was assessed by the SUNsET assay, and 47S pre-rRNA transcription was determined by transfection of a 47S gene promoter-reporter plasmid. BMP7 treatment increased protein translational capacity. This was associated by increased 18S and 5.8S rRNA and NKX3-2 mRNA expression, as well as increased 47S gene promotor activity. Knockdown of NKX3-2 led to increased expression of RUNX2, accompanied by decreased 47S gene promotor activity and rRNA expression, an effect BMP7 was unable to restore. Our data demonstrate that BMP7 positively influences protein translation capacity of SW1353 cells and chondrocytes. This is likely caused by an NKX3-2-dependent activation of 47S gene promotor activity. This finding connects morphogen-mediated changes in cellular differentiation to an aspect of ribosome biogenesis via key transcription factors central to determining the chondrocyte phenotype. |
| Databáze: | OpenAIRE |
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