Increased Synovial CD14 mRNA Expression and Proportion of CD14high Subsets in Early-Stage Hip Osteoarthritis: Propensity Matched Score Analysis

Ohashi, Y; Uchida, Kentaro; Fukushima, Kazuhiko; Satoh, Masashi; Koyama, Tomohisa; Tsuchiya, Maho; Saito, Hiroki; Uchiyama, Katsufumi; Takahira, Naonobu; Inoue, Gen; Takaso, Masashi

doi:10.3390/ijms232113622

Cited by 5 publications

(3 citation statements)

References 39 publications

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“…Importantly, the contribution of CD39−CD55+ cells may be more significant in the early stages of OA, where synovitis plays a crucial role in driving pain [44]. As OA advances, the inflammatory response tends to diminish [45,46], potentially diminishing the impact of this fibroblast subset in late-stage OA. To fully elucidate the role of fibroblast subtypes across different OA stages, further investigations utilizing synovial tissue from early OA patients are warranted.…”

Section: Discussionmentioning

confidence: 99%

CD39+CD55− Fb Subset Exhibits Myofibroblast-Like Phenotype and Is Associated with Pain in Osteoarthritis of the Knee

Tsuchiya,

Ohashi,

Kodera

et al. 2023

Biomedicines

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Recent studies utilizing single-cell analysis have unveiled the presence of various fibroblast (Fb) subsets within the synovium under inflammatory conditions in osteoarthritis (OA), distinguishing them from those in rheumatoid arthritis (RA). Moreover, it has been reported that pain in knee OA patients is linked to specific fibroblast subsets. Single-cell expression profiling methods offer an incredibly detailed view of the molecular states of individual cells. However, one limitation of these methods is that they require the destruction of cells during the analysis process, rendering it impossible to directly assess cell function. In our study, we employ flow cytometric analysis, utilizing cell surface markers CD39 and CD55, in an attempt to isolate fibroblast subsets and investigate their relationship with OA pathology. Synovial tissues were obtained from 25 knee OA (KOA) patients. Of these, six samples were analyzed by RNA-seq (n = 3) and LC/MS analysis (n = 3). All 25 samples were analyzed to estimate the proportion of Fb (CD45−CD31−CD90+) subset by flow cytometry. The proportion of Fb subsets (CD39+CD55− and CD39−CD55+) and their association with osteoarthritis pathology were evaluated. CD39+CD55− Fb highly expressed myogenic markers such as CNN1, IGFBP7, MYH11, and TPM1 compared to CD39−CD55+ Fb. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of upregulated differentially expressed genes (DEGs) in CD39+CD55− Fb identified the Apelin pathway and cGMP-PKC-signaling pathway as possibly contributing to pain. LC/MS analysis indicated that proteins encoded by myogenic marker genes, including CNN1, IGFBP7, and MYH11, were also significantly higher than in CD39−CD55+ Fb. CD39−CD55+ Fb highly expressed PRG4 genes and proteins. Upregulated DEGs were enriched for pathways associated with proinflammatory states (‘RA’, ‘TNF signaling pathway’, ‘IL-17 signaling pathway’). The proportion of CD39+CD55− Fb in synovium significantly correlated with both resting and active pain levels in knee OA (KOA) patients (resting pain, ρ = 0.513, p = 0.009; active pain, ρ = 0.483, p = 0.015). There was no correlation between joint space width (JSW) and the proportion of CD39+CD55− Fb. In contrast, there was no correlation between the proportion of CD39−CD55+ Fb and resting pain, active pain, or JSW. In conclusion, CD39+CD55− cells exhibit a myofibroblast phenotype, and its proportion is associated with KOA pain. Our study sheds light on the potential significance of CD39+CD55− synovial fibroblasts in osteoarthritis, their myofibroblast-like phenotype, and their association with joint pain. These findings provide a foundation for further research into the mechanisms underlying fibrosis, the impact of altered gene expression on osteoarthritic joints, and potential therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

CD39+CD55− Fb Subset Exhibits Myofibroblast-Like Phenotype and Is Associated with Pain in Osteoarthritis of the Knee

Tsuchiya,

Ohashi,

Kodera

et al. 2023

Biomedicines

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“…Activation of Toll-like receptor (TLR) signal on monocytes induces production of proinflammatory cytokines/ chemokines and transmission of pain signals. [ 28 , 29 ] A recent study has shown that the typical response of CD14CD16 monocytes to knee synovial derived mediators is a key target for overcoming the onset and progression of osteoarthritis. [ 30 ] TLR pathway plays an important role in OA inflammation.…”

Section: Discussionmentioning

confidence: 99%

The role of CD14 and CSF1R in osteoarthritis and gastritis

Zheng,

Li,

Feng

et al. 2023

Medicine

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Osteoarthritis (OA) is a non-inflammatory degenerative joint disease that mainly involves articular cartilage damage and involves the whole joint tissue. Gastritis is a common stomach disorder, typically referring to inflammation or lesions of the gastric mucosa. However, the relationship between CD14 and colony stimulating factor-1 receptor (CSF1R) and these 2 diseases is not yet clear. OA datasets GSE46750, GSE82107 and gastritis datasets GSE54043 profiles were downloaded from gene expression omnibus databases generated by GPL10558 and GPL570.The R package limma was used to screen differentially expressed genes (DEGs). Weighted gene co-expression network analysis was performed. The construction and analysis of protein–protein interaction network, functional enrichment analysis, gene set enrichment analysis and comparative toxicogenomics database analysis were performed. TargetScan was used to screen miRNAs regulating central DEGs. A total of 568 DEGs were identified. According to the gene ontology (GO) and biological processes analysis, they were mainly enriched in ATP metabolism negative regulation, toll-like receptor TLR1:TLR2 signaling pathway, and intracellular transport. The enrichment terms for OA and gastritis were similar to the GO and Kyoto encyclopedia of gene and genome enrichment terms of DEGs, mainly enriched in ATP metabolism negative regulation, secretion granules, transmembrane receptor protein kinase activity, cytokine–cytokine receptor interaction, Toll-like receptor signaling pathway, MAPK signaling pathway, and TGF-β signaling pathway. In the Metascape enrichment projects, GO enrichment projects showed functions related to cell–cell receptor interaction, cell secretion, and growth. Two core genes were identified through the construction and analysis of the protein–protein interaction network. The core genes (CD14 and CSF1R) exhibited high expression in OA and gastritis samples and low expression in normal samples. Comparative toxicogenomics database analysis revealed associations between core genes (CD14 and CSF1R) and diseases such as OA, osteoporosis, gastritis, juvenile arthritis, diarrhea, and inflammation. CD14 and CSF1R are highly expressed in OA and gastritis, making them potential therapeutic targets for both diseases.

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“…The femoral bone contour served as the starting point for JSW measurement, while the reference line for the tibial mid-coronal plane was established by connecting the medial and lateral edges of the tibia. Pain evaluations, including VAS-R and VAS-M, were conducted during the preoperative periods using the standard 10-point VAS, where each point represents 10 mm on the scale (ranging from 0 mm for no pain to 100 mm for the worst imaginable pain) [50]. Clinical assessments were performed at our outpatient facility a month before each surgical intervention.…”

Section: Correlation Between Proportion Of Entpd1+cd55+ Cells and Oa ...mentioning

confidence: 99%

Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium

Tsuchiya,

Ohashi,

Fukushima

et al. 2024

IJMS

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Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by cartilage erosion, structural changes, and inflammation. Synovial fibroblasts play a crucial role in OA pathophysiology, with abnormal fibroblastic cells contributing significantly to joint pathology. Fibrocytes, expressing markers of both hematopoietic and stromal cells, are implicated in inflammation and fibrosis, yet their marker and role in OA remain unclear. ENTPD1, an ectonucleotidase involved in purinergic signaling and expressed in specific fibroblasts in fibrotic conditions, led us to speculate that ENTPD1 plays a role in OA pathology by being expressed in fibrocytes. This study aimed to investigate the phenotype of ENTPD1+CD55+ and ENTPD1−CD55+ synovial fibroblasts in OA patients. Proteomic analysis revealed a distinct molecular profile in ENTPD1+CD55+ cells, including the upregulation of fibrocyte markers and extracellular matrix-related proteins. Pathway analysis suggested shared mechanisms between OA and rheumatoid arthritis. Correlation analysis revealed an association between ENTPD1+CD55+ fibrocytes and resting pain in OA. These findings highlight the potential involvement of ENTPD1 in OA pain and suggest avenues for targeted therapeutic strategies. Further research is needed to elucidate the underlying molecular mechanisms and validate potential therapeutic targets.

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Increased Synovial CD14 mRNA Expression and Proportion of CD14high Subsets in Early-Stage Hip Osteoarthritis: Propensity Matched Score Analysis

Cited by 5 publications

References 39 publications

CD39+CD55− Fb Subset Exhibits Myofibroblast-Like Phenotype and Is Associated with Pain in Osteoarthritis of the Knee

CD39+CD55− Fb Subset Exhibits Myofibroblast-Like Phenotype and Is Associated with Pain in Osteoarthritis of the Knee

The role of CD14 and CSF1R in osteoarthritis and gastritis

Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium

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