Inflammation and angiogenesis,the major pathological changes of osteoarthritis(OA),are closely associated with joint pain;however,pertinent signalling interactions within subchondral bone of osteoarthritic joints and ...Inflammation and angiogenesis,the major pathological changes of osteoarthritis(OA),are closely associated with joint pain;however,pertinent signalling interactions within subchondral bone of osteoarthritic joints and potential contribution to the peripheral origin of OA pain remain to be elucidated.Herein we developed a unilateral anterior crossbite mouse model with osteoarthritic changes in the temporomandibular joint.Microarray-based transcriptome analysis,besides quantitative real-time polymerase chain reaction,was performed to identify differentially expressed genes(DEGs).Overall,182 DEGs(fold change≥2,P<0.05)were identified between the control and unilateral anterior crossbite groups:168 were upregulated and 14 were downregulated.On subjecting significant DEGs to enrichment analyses,inflammation and angiogenesis were identified as the most affected.Inflammation-related DEGs were mainly enriched in T cell activation and differentiation and in the mammalian target of rapamycin/nuclear factor-κB/tumour necrosis factor signalling.Furthermore,angiogenesis-related DEGs were mainly enriched in the Gene Ontology terms angiogenesis regulation and vasculature development and in the KEGG pathways of phosphoinositide 3-kinase-protein kinase B/vascular endothelial growth factor/hypoxia-inducible factor 1 signalling.Protein-protein interaction analysis revealed a close interaction between inflammation-and angiogenesis-related DEGs,suggesting that phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(Pi3kcd),cathelicidin antimicrobial peptide(Camp),C-X-C motif chemokine receptor 4(Cxcr4),and MYB proto-oncogene transcription factor(Myb)play a central role in their interaction.To summarize,our findings reveal that in subchondral bone of osteoarthritic joints,signal interaction is interrelated between inflammation and angiogenesis and associated with the peripheral origin of OA pain;moreover,our data highlight potential targets for the inhibition of OA pain.展开更多
基金supported by the National Key Research and development Programme,No.2023YFC2509100National Natural Science Foundation of China,No.82170978Distinguished Young Scientists Funds of Shaanxi Province,No.2021JC-34(all to JK).
文摘Inflammation and angiogenesis,the major pathological changes of osteoarthritis(OA),are closely associated with joint pain;however,pertinent signalling interactions within subchondral bone of osteoarthritic joints and potential contribution to the peripheral origin of OA pain remain to be elucidated.Herein we developed a unilateral anterior crossbite mouse model with osteoarthritic changes in the temporomandibular joint.Microarray-based transcriptome analysis,besides quantitative real-time polymerase chain reaction,was performed to identify differentially expressed genes(DEGs).Overall,182 DEGs(fold change≥2,P<0.05)were identified between the control and unilateral anterior crossbite groups:168 were upregulated and 14 were downregulated.On subjecting significant DEGs to enrichment analyses,inflammation and angiogenesis were identified as the most affected.Inflammation-related DEGs were mainly enriched in T cell activation and differentiation and in the mammalian target of rapamycin/nuclear factor-κB/tumour necrosis factor signalling.Furthermore,angiogenesis-related DEGs were mainly enriched in the Gene Ontology terms angiogenesis regulation and vasculature development and in the KEGG pathways of phosphoinositide 3-kinase-protein kinase B/vascular endothelial growth factor/hypoxia-inducible factor 1 signalling.Protein-protein interaction analysis revealed a close interaction between inflammation-and angiogenesis-related DEGs,suggesting that phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(Pi3kcd),cathelicidin antimicrobial peptide(Camp),C-X-C motif chemokine receptor 4(Cxcr4),and MYB proto-oncogene transcription factor(Myb)play a central role in their interaction.To summarize,our findings reveal that in subchondral bone of osteoarthritic joints,signal interaction is interrelated between inflammation and angiogenesis and associated with the peripheral origin of OA pain;moreover,our data highlight potential targets for the inhibition of OA pain.
