The role of accelerated growth plate fusion in the absence of SOCS2 on osteoarthritis vulnerability

Samvelyan, Hasmik Jasmine; Huesa, Carmen; Lin, Chan‐Yu; Farquharson, Colin; Staines, Katherine

doi:10.1302/2046-3758.113.bjr-2021-0259.r1

Cited by 5 publications

(4 citation statements)

References 36 publications

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“…It has been reported that SOCS2 suppresses the inflammatory response, reducing chondrocyte apoptosis, and inhibiting the progression of osteoarthritis ( Zhang et al, 2021 ). In addition, enhanced GH signaling via SOCS2 deletion accelerated growth plate fusion ( Samvelyan et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics gene analysis of potential biomarkers and therapeutic targets of osteoarthritis associated myelodysplastic syndrome

Xin

Li²,

Dong³

et al. 2023

Front. Genet.

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Objective: Osteoarthritis (OA) and Myelodysplastic syndrome (MDS) are diseases caused by the same immune disorder with unclear etiology and many similarities in clinical manifestations; however, the specific mechanisms between osteoarthritis and myelodysplastic syndrome are unclear.Methods: The expression profile microarrays of osteoarthritis and myelodysplastic syndrome were searched in the GEO database, the intersection of their differential genes was taken, Venn diagrams were constructed to find common pathogenic genes, bioinformatics analysis signaling pathway analysis was performed on the obtained genes, and protein-protein interaction networks were constructed to find hub genes in order to establish diagnostic models for each disease and explore the immune infiltration of hub genes.Results: 52 co-pathogenic genes were screened for association with immune regulation, immune response, and inflammation. The mean area under the receiver operating characteristic (ROC) for all 10 genes used for co-causal diagnosis ranged from 0.71–0.81. Immune cell infiltration analysis in the myelodysplastic syndrome subgroup showed that the relative numbers of Macrophages M1, B cells memory, and T cells CD4 memory resting in the myelodysplastic syndrome group were significantly different from the normal group, however, in the osteoarthritis subgroup the relative numbers of Mast cells resting in the osteoarthritis subgroup was significantly different from the normal group.Conclusion: There are common pathogenic genes in osteoarthritis and myelodysplastic syndrome, which in turn mediate differential alterations in related signaling pathways and immune cells, affecting the high prevalence of osteoarthritis and myelodysplastic syndrome and the two disease phenomena.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics gene analysis of potential biomarkers and therapeutic targets of osteoarthritis associated myelodysplastic syndrome

Xin

Li²,

Dong³

et al. 2023

Front. Genet.

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“…These findings make SOCS2 a candidate for further studies and the activation of more robust SOCS2 expression could be a goal for future therapeutic development. The regulatory role of SOCS2 in chondrocytes is likely to be subtle, as SOCS2 knockout mice did not show altered OA development 64 . Because this study used a global germline deletion, other members of the inflammatory cascade may have compensated for SOCS2 loss, and it would be interesting to learn whether the inducible loss of SOCS2 in adult chondrocytes would generate a different result.…”

Section: Discussionmentioning

confidence: 99%

“…In situ Hi-C was performed as previously described 64 . Pellets were lysed in ice-cold Hi-C lysis buffer (10mM Tris-HCl pH 8.0, 10mM NaCl, 0.2% IGEPAL CA630) with 50μL of protease inhibitors for 15 min on ice.…”

Section: Hi-cmentioning

confidence: 99%

3D Chromatin Structure in Chondrocytes Identifies Putative Osteoarthritis Risk Genes

Thulson

Davis

D’Costa

et al. 2022

Preprint

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Genome-wide association studies (GWAS) have identified over 100 loci associated with osteoarthrtis (OA) risk, but the majority of OA risk variants are non-coding, making it difficult to identify the impacted genes for further study and therapeutic development. To address this need, we used a multi-omic approach and genome editing to identify and functionally characterize potential OA risk genes. Computational analysis of GWAS and ChIP-seq data revealed that chondrocyte regulatory loci are enriched for OA risk variants. We constructed a chondrocyte specific regulatory network by mapping 3D chromatin structure and active enhancers in human chondrocytes. We then intersected these data with our previously collected RNA-seq dataset of chondrocytes responding to fibronectin fragment (FN-f), a known OA trigger. Integration of the three genomic datasets with recently reported OA GWAS variants revealed a refined set of putative causal OA variants and their potential target genes. One of the novel putative target genes identified was SOCS2, which was connected to a putative causal variant by a 170 Kb loop and is differentially regulated in response to FN-f. CRISPR-Cas9-mediated deletion of SOCS2 in primary human chondrocytes from three independent donors led to heightened expression of inflammatory markers after FN-f treatment. These data suggest that SOCS2 plays a role in resolving inflammation in response to cartilage matrix damage and provides a possible mechanistic explanation for its influence on OA risk. In total, we identified 56 unique putative OA risk genes for further research and potential therapeutic development.

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“…The suppressor of cytokine signaling 2 (SOCS2), one of the members of the suppressor of cytokine signaling family glycoproteins, is an intracellular suppressor of the GH signaling pathway [ 31 ]. SOCS2-deficient mice that enhanced GH signaling pathway created wider proliferative zones of the growth plates [ 32 ].…”

Section: Overview Of the Factors Maintaining The Growth Platementioning

confidence: 99%

Roles of Local Soluble Factors in Maintaining the Growth Plate: An Update

Zhang

Ahmadpoor

Lin

2023

Genes

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The growth plate is a cartilaginous tissue found at the ends of growing long bones, which contributes to the lengthening of bones during development. This unique structure contains at least three distinctive layers, including resting, proliferative, and hypertrophic chondrocyte zones, maintained by a complex regulatory network. Due to its soft tissue nature, the growth plate is the most susceptible tissue of the growing skeleton to injury in childhood. Although most growth plate damage in fractures can heal, some damage can result in growth arrest or disorder, impairing leg length and resulting in deformity. In this review, we re-visit previously established knowledge about the regulatory network that maintains the growth plate and integrate current research displaying the most recent progress. Next, we highlight local secretary factors, such as Wnt, Indian hedgehog (Ihh), and parathyroid hormone-related peptide (PTHrP), and dissect their roles and interactions in maintaining cell function and phenotype in different zones. Lastly, we discuss future research topics that can further our understanding of this unique tissue. Given the unmet need to engineer the growth plate, we also discuss the potential of creating particular patterns of soluble factors and generating them in vitro.

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The role of accelerated growth plate fusion in the absence of SOCS2 on osteoarthritis vulnerability

Cited by 5 publications

References 36 publications

Bioinformatics gene analysis of potential biomarkers and therapeutic targets of osteoarthritis associated myelodysplastic syndrome

Bioinformatics gene analysis of potential biomarkers and therapeutic targets of osteoarthritis associated myelodysplastic syndrome

3D Chromatin Structure in Chondrocytes Identifies Putative Osteoarthritis Risk Genes

Roles of Local Soluble Factors in Maintaining the Growth Plate: An Update

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