Universität zu Köln

Georgieva, Veronika S., Bluhm, Bjoern, Probst, Kristina, Zhu, Mengjie, Heilig, Juliane, Niehoff, Anja and Brachvogel, Bent (2022). Ablation of the miRNA cluster 24 in cartilage and osteoblasts impairs bone remodeling. Sci Rep, 12 (1). BERLIN: NATURE PORTFOLIO. ISSN 2045-2322

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Georgieva, Veronika S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bluhm, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Probst, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhu, Mengjie UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilig, Juliane UNSPECIFIED UNSPECIFIED UNSPECIFIED Niehoff, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-666244
DOI:	10.1038/s41598-022-13231-z
Journal or Publication Title:	Sci Rep
Volume:	12
Number:	1
Date:	2022
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION; GROWTH-PLATE; CHONDROCYTES; CELLS; OSTEOCLASTOGENESIS; OSTEOPROTEGERIN; OSSIFICATION; MICRORNAS; MIR-322; LIGAND Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66624