Ablation of the miRNA cluster 24 in cartilage and osteoblasts impairs bone remodeling
Abstract MicroRNAs (miRNAs) post-transcriptionally regulate cartilage and bone development and function, however, only few miRNAs have been described to play a role for cartilage to bone transition in vivo. Previously, we showed that cartilage-specific deletion of the Mirc24 cluster in newborn male...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13231-z |
| _version_ | 1811256981833383936 |
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| author | Veronika S. Georgieva Björn Bluhm Kristina Probst Mengjie Zhu Juliane Heilig Anja Niehoff Bent Brachvogel |
| author_facet | Veronika S. Georgieva Björn Bluhm Kristina Probst Mengjie Zhu Juliane Heilig Anja Niehoff Bent Brachvogel |
| author_sort | Veronika S. Georgieva |
| collection | DOAJ |
| description | Abstract MicroRNAs (miRNAs) post-transcriptionally regulate cartilage and bone development and function, however, only few miRNAs have been described to play a role for cartilage to bone transition in vivo. Previously, we showed that cartilage-specific deletion of the Mirc24 cluster in newborn male mice leads to impaired growth plate cartilage development due to increased RAF/MEK/ERK signaling and affects the stability of the cartilage extracellular matrix on account of decreased SOX6 and SOX9 and increased MMP13 levels. Here, we studied how Mirc24 cluster inactivation in cartilage and osteoblasts leads to an increased bone density associated with defects in collagen remodeling in trabecular bone. No changes in osteoblast distribution were observed, whereas the number of osteoclasts was reduced and TRAP activity in osteoclasts decreased. Surprisingly, an increased level of cluster-encoded miR-322 or miR-503 raises Rankl gene expression and inactivation of the cluster in chondrocytes reduces Rankl expression. These results suggest that the Mirc24 cluster regulates Rankl expression in chondrocytes at the chondro-osseous border, where the cluster is mainly expressed to modulate osteoclast formation, bone remodeling and bone integrity. |
| first_indexed | 2024-04-12T17:49:30Z |
| format | Article |
| id | doaj.art-f80ad3cb2e664fc8b1a238dca0a0434f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T17:49:30Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f80ad3cb2e664fc8b1a238dca0a0434f2022-12-22T03:22:32ZengNature PortfolioScientific Reports2045-23222022-06-0112111110.1038/s41598-022-13231-zAblation of the miRNA cluster 24 in cartilage and osteoblasts impairs bone remodelingVeronika S. Georgieva0Björn Bluhm1Kristina Probst2Mengjie Zhu3Juliane Heilig4Anja Niehoff5Bent Brachvogel6Center for Biochemistry, Faculty of Medicine, University of CologneCenter for Biochemistry, Faculty of Medicine, University of CologneCenter for Biochemistry, Faculty of Medicine, University of CologneCenter for Biochemistry, Faculty of Medicine, University of CologneInstitute of Biomechanics and Orthopaedics, German Sport University CologneInstitute of Biomechanics and Orthopaedics, German Sport University CologneCenter for Biochemistry, Faculty of Medicine, University of CologneAbstract MicroRNAs (miRNAs) post-transcriptionally regulate cartilage and bone development and function, however, only few miRNAs have been described to play a role for cartilage to bone transition in vivo. Previously, we showed that cartilage-specific deletion of the Mirc24 cluster in newborn male mice leads to impaired growth plate cartilage development due to increased RAF/MEK/ERK signaling and affects the stability of the cartilage extracellular matrix on account of decreased SOX6 and SOX9 and increased MMP13 levels. Here, we studied how Mirc24 cluster inactivation in cartilage and osteoblasts leads to an increased bone density associated with defects in collagen remodeling in trabecular bone. No changes in osteoblast distribution were observed, whereas the number of osteoclasts was reduced and TRAP activity in osteoclasts decreased. Surprisingly, an increased level of cluster-encoded miR-322 or miR-503 raises Rankl gene expression and inactivation of the cluster in chondrocytes reduces Rankl expression. These results suggest that the Mirc24 cluster regulates Rankl expression in chondrocytes at the chondro-osseous border, where the cluster is mainly expressed to modulate osteoclast formation, bone remodeling and bone integrity.https://doi.org/10.1038/s41598-022-13231-z |
| spellingShingle | Veronika S. Georgieva Björn Bluhm Kristina Probst Mengjie Zhu Juliane Heilig Anja Niehoff Bent Brachvogel Ablation of the miRNA cluster 24 in cartilage and osteoblasts impairs bone remodeling Scientific Reports |
| title | Ablation of the miRNA cluster 24 in cartilage and osteoblasts impairs bone remodeling |
| title_full | Ablation of the miRNA cluster 24 in cartilage and osteoblasts impairs bone remodeling |
| title_fullStr | Ablation of the miRNA cluster 24 in cartilage and osteoblasts impairs bone remodeling |
| title_full_unstemmed | Ablation of the miRNA cluster 24 in cartilage and osteoblasts impairs bone remodeling |
| title_short | Ablation of the miRNA cluster 24 in cartilage and osteoblasts impairs bone remodeling |
| title_sort | ablation of the mirna cluster 24 in cartilage and osteoblasts impairs bone remodeling |
| url | https://doi.org/10.1038/s41598-022-13231-z |
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