Identification of genes and pathways associated with subchondral bone in osteoarthritis via bioinformatic analysis

Abstract

Osteoarthritis (OA) is a high prevalent musculoskeletal problem, which can cause severe pain, constitute a huge social and economic burden, and seriously damage the quality of life. This study was intended to identify genetic characteristics of subchondral bone in patients with OA and to elucidate the potential molecular mechanisms involved. Data of gene expression profiles (GSE51588), which contained 40 OA samples and 10 normal samples, was obtained from the Gene Expression Omnibus (GEO). The raw data were integrated to obtain differentially expressed genes (DEGs) and were further analyzed with bioinformatic analysis. The protein–protein interaction (PPI) networks were built and analyzed via Search Tool for the Retrieval of Interacting Genes (STRING). The significant modules and hub genes were identified via Cytoscape. Moreover, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis were performed. Totally 235 DEGs were differentially expressed in the subchondral bone from OA patients compared with those of normal individuals, of which 78 were upregulated and 157 were downregulated. Eight hub genes were identified, including DEFA4, ARG1, LTF, RETN, PGLYRP1, OLFM4, ORM1, and BPI. The enrichment analyses of the DEGs and significant modules indicated that DEGs were mainly involved in inflammatory response, extracellular space, RAGE receptor binding, and amoebiasis pathway. The present study provides a novel and in-depth understanding of pathogenesis of the OA subchondral bone at molecular level. DEFA4, ARG1, LTF, RETN, PGLYRP1, OLFM4, ORM1, and BPI may be the new candidate targets for diagnosis and therapies on patients with OA in the future.

Comprehensive bulk and single-cell transcriptome profiling give useful insights into the characteristics of osteoarthritis associated synovial macrophages

“…KEGG enrichment analysis results showed that the 172 common DEGs were mainly involved in immune-related pathways, such as Rheumatoid arthritis, NF-kappaB signaling pathway, Osteoclast differentiation, TNF signaling pathway, MAPK signaling pathway, and T-cell receptor signaling pathway (Figure 1F; Table S3). These results were consistent with the previous results and demonstrated the aberrant expression of these genes lead to inflammatory response in OA synovitis tissues (42,43). On the other hands, we performed the clustering analysis of these DEGs for further clearly specific function using Metascape software (Figure 1G), and these genes mainly enriched and clustered eight categories, including inflammatory response, regulation of MAPK cascade, Pid Atf2 pathway, Thythmic process, response to extracellular stimulus, response to corticosteroid, multicellular organism process, and response to growth factor.…”

Differential Gene Expression Involved in Bone Turnover of Mice Expressing Constitutively Active TGFβ Receptor Type I

“…The results of qPCR analysis showed that 9 upregulated genes, Pdzk1 , Vpreb1a , Cd72 , Igll1 , Tnfrsf19 , Gas6 , Zdhhc2 , Igfbp4 , and Hdac7, were significantly increased, and 10 downregulated genes, Dhcr24 , Padi4 , Gsr , Clec4d , Lilrb4a , Clec4e , Fcgr4 , Stfa2 , Olfm4 , and Cxcr1, were significantly decreased in Mx1;TβRI CA compared to the WT group ( Figure 4 A,B). The functions of these 19 DEGs are briefly described in Supplementary Tables S1 and S2 [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”

Transcriptome Sequencing Identifies Abnormal lncRNAs and mRNAs and Reveals Potentially Hub Immune-Related mRNA in Osteoporosis with Vertebral Fracture

“…Peptidoglycan recognition protein 1 (PGLYRP1) plays a role in innate immunity and has bacteriostatic activity. Yang et al 46 identified it work as a hub mRNA of the osteoarthritis subchondral bone. Our research shows that it is also a hub mRNA regulated by lncRNA in osteoporosis.…”