Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis
IntroductionEvidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis...
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1251034/full |
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| author | Lucas Peixoto Sales Bidossessi Wilfried Hounkpe Mariana Ortega Perez Valéria Falco Caparbo Diogo Souza Domiciano Eduardo Ferreira Borba Georg Schett Camille Pinto Figueiredo Rosa Maria Rodrigues Pereira |
| author_facet | Lucas Peixoto Sales Bidossessi Wilfried Hounkpe Mariana Ortega Perez Valéria Falco Caparbo Diogo Souza Domiciano Eduardo Ferreira Borba Georg Schett Camille Pinto Figueiredo Rosa Maria Rodrigues Pereira |
| author_sort | Lucas Peixoto Sales |
| collection | DOAJ |
| description | IntroductionEvidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion.MethodsThirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina® platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways.ResultsRNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (LARP6) and bone formation process (PAPPA) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions.ConclusionThese findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients. |
| first_indexed | 2024-03-11T19:41:58Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T19:41:58Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dd22dc6de239467aa6063bb6c081bee12023-10-06T10:08:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12510341251034Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid ArthritisLucas Peixoto Sales0Bidossessi Wilfried Hounkpe1Mariana Ortega Perez2Valéria Falco Caparbo3Diogo Souza Domiciano4Eduardo Ferreira Borba5Georg Schett6Camille Pinto Figueiredo7Rosa Maria Rodrigues Pereira8Rheumatology Division, Bone Metabolism Laboratory, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilRheumatology Division, Bone Metabolism Laboratory, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilRheumatology Division, Bone Metabolism Laboratory, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilRheumatology Division, Bone Metabolism Laboratory, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilRheumatology Division, Bone Metabolism Laboratory, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilRheumatology Division, Bone Metabolism Laboratory, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilDepartment of Internal Medicine 3-Rheumatology and Immunology, Friedrich Alexander Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, GermanyRheumatology Division, Bone Metabolism Laboratory, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilRheumatology Division, Bone Metabolism Laboratory, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilIntroductionEvidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion.MethodsThirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina® platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways.ResultsRNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (LARP6) and bone formation process (PAPPA) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions.ConclusionThese findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1251034/fullrheumatoid arthritisclassical monocytesbone erosionsinflammationbone formation |
| spellingShingle | Lucas Peixoto Sales Bidossessi Wilfried Hounkpe Mariana Ortega Perez Valéria Falco Caparbo Diogo Souza Domiciano Eduardo Ferreira Borba Georg Schett Camille Pinto Figueiredo Rosa Maria Rodrigues Pereira Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis Frontiers in Immunology rheumatoid arthritis classical monocytes bone erosions inflammation bone formation |
| title | Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis |
| title_full | Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis |
| title_fullStr | Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis |
| title_full_unstemmed | Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis |
| title_short | Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis |
| title_sort | transcriptomic characterization of classical monocytes highlights the involvement of immuno inflammation in bone erosion in rheumatoid arthritis |
| topic | rheumatoid arthritis classical monocytes bone erosions inflammation bone formation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1251034/full |
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