Defects in chondrocyte maturation and secondary ossification in mouse knee joint epiphyses due to Snorc deficiency

Heinonen, J.; Zhang, F.-P.; Surmann‐Schmitt, Cordula; Honkala, Sanna Maria; Stöck, Michael; Poutanen, Matti; Säämänen, Anna‐Marja

doi:10.1016/j.joca.2017.03.010

Cited by 7 publications

(5 citation statements)

References 48 publications

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“…Tissue samples were pulverized in liquid nitrogen and homogenized in TRIsure (Bioline) for RNA isolation ( Heinonen et al, 2017 ). RNA concentration was measured using Nanodrop One (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

Multiple targets identified with genome wide profiling of small RNA and mRNA expression are linked to fracture healing in mice

et al. 2021

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Long-bone fracture is a common injury and its healing process at the fracture site involves several overlapping phases, including inflammation, migration of mesenchymal progenitors into the fracture site, endochondral ossification, angiogenesis and finally bone remodelling. Increasing evidence shows that small noncoding RNAs are important regulators of chondrogenesis, osteogenesis and fracture healing. MicroRNAs are small single-stranded, non-coding RNA-molecules intervening in most physiological and biological processes, including fracture healing. Angiogenin-cleaved 5′ tRNA halves, also called as tiRNAs (stress-induced RNAs) have been shown to repress protein translation. In order to gain further understanding on the role of small noncoding RNAs in fracture healing, genome wide expression profiles of tiRNAs, miRNAs and mRNAs were followed up to 14 days after fracture in callus tissue of an in vivo mouse model with closed tibial fracture and, compared to intact bone and articular cartilage at 2 months of age. Total tiRNA expression level in cartilage was only approximately one third of that observed in control D0 bone. In callus tissue, 11 mature 5′end tiRNAs out of 191 tiRNAs were highly expressed, and seven of them were differentially expressed during fracture healing. When comparing the control tissues, 25 miRNAs characteristic to bone and 29 miRNAs characteristic to cartilage tissue homeostasis were identified. Further, a total of 54 out of 806 miRNAs and 5420 out of 18,700 mRNAs were differentially expressed (DE) in callus tissue during fracture healing and, in comparison to control bone. They were associated to gene ontology processes related to mesenchymal tissue development and differentiation. A total of 581 miRNA-mRNA interactions were identified for these 54 DE miRNAs by literature searches in PubMed, thereby linking by Spearman correlation analysis 14 downregulated and 28 upregulated miRNAs to 164 negatively correlating and 168 positively correlating miRNA-mRNA pairs with chondrogenic and osteogenic phases of fracture healing. These data indicated that tiRNAs and miRNAs were differentially expressed in fracture callus tissue, suggesting them important physiological functions during fracture healing. Hence, the data provided by this study may contribute to future clinical applications, such as potential use as biomarkers or as tools in the development of novel therapeutic approaches for fracture healing.

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Section: Methodsmentioning

confidence: 99%

Multiple targets identified with genome wide profiling of small RNA and mRNA expression are linked to fracture healing in mice

et al. 2021

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“…In addition, different degrees of OA severity should be included in further experiments as well as in vivo experiments with osteoarthritic animals, also to test different application methods for rhuGSN, like intra synovial applications. Further additional analyses of proteins such as Snorc (small cartilage-rich novel), a specific trans membrane proteoglycan involved in endochondral ossification [ 30 ], or other factors such as fibronectin [ 31 ] should be included in further experiments to understand how accurate the positive effect of rhuGSN is in chondrocytes. New experiments with 3D models [ 32 ] and tissue samples for the cultivation of chondrocytes [ 33 ] could provide more detailed insight into how rhuGSN affects chondrocytes and the surrounding extracellular matrix.…”

Section: Discussionmentioning

confidence: 99%

Recombinant human gelsolin promotes the migration of human articular cartilage chondrocytes by regulating gene expression in vitro

Feldt

Welss

Schropp

et al. 2020

Osteoarthritis and Cartilage Open

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“…5f), a number of non-TF genes with roles in cartilage makeup and chondrocyte differentiation (COL27A1, PRKCA, SNORC, CRISPLD2) were identified and predicted to be regulated by NFATC1 and FOXA3. COL27A1, and the proteoglycan SNORC, are involved in chondrocyte ECM makeup and maturation 93 .…”

Section: Developmental Links To Complex Traits Of the Adult Skeletonmentioning

confidence: 99%

A multiomic atlas of human early skeletal development

To,

Fei,

Pett

et al. 2024

Preprint

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Bone and joint formation in the developing skeleton rely on co-ordinated differentiation of progenitors in the nascent developing limbs and joints. The cell states, epigenetic processes and key regulatory factors underlying their lineage commitment to osteogenic and other mesenchymal populations during ossification and joint formation remain poorly understood and are largely unexplored in human studies. Here, we apply paired single-nuclei transcriptional and epigenetic profiling of 336,000 droplets, in addition to spatial transcriptomics, to construct a comprehensive atlas of human bone, cartilage and joint development in the shoulder, hip, knee and cranium from 5 to 11 post-conception weeks. Spatial mapping of cell clusters to our highly multiplexed in situ sequencing (ISS) data using our newly developed tool ISS-Patcher revealed new cellular mechanisms of zonation during bone and joint formation. Combined modelling of chromatin accessibility and RNA expression allowed the identification of the transcriptional and epigenetic regulatory landscapes that drive differentiation of mesenchymal lineages including osteogenic and chondrogenic lineages, and novel chondrocyte cell states. In particular, we define regionally distinct limb and cranial osteoprogenitor populations and trajectories across the fetal skeleton and characterise differential regulatory networks that govern intramembranous and endochondral ossification. Through somatic mutation analysis, we predict two new potential cell origins for human chondrocyte development. We also introduce SNP2Cell, a tool to link cell-type specific regulatory networks to numerous polygenic traits such as osteoarthritis. We also conduct in silico perturbations of genes that cause monogenic craniosynostosis and implicate potential pathogenic cell states and disease mechanisms involved. This work forms a detailed and dynamic regulatory atlas of human fetal skeletal maturation and advances our fundamental understanding of cell fate determination in human skeletal development.

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Defects in chondrocyte maturation and secondary ossification in mouse knee joint epiphyses due to Snorc deficiency

Abstract: These findings suggest a role of Snorc in regulation of chondrocyte maturation and postnatal endochondral ossification. The interaction identified between recombinant Snorc core protein and FGF2 suggest functions related to FGF signaling.

Cited by 7 publications

References 48 publications

Multiple targets identified with genome wide profiling of small RNA and mRNA expression are linked to fracture healing in mice

Multiple targets identified with genome wide profiling of small RNA and mRNA expression are linked to fracture healing in mice

Recombinant human gelsolin promotes the migration of human articular cartilage chondrocytes by regulating gene expression in vitro

A multiomic atlas of human early skeletal development

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