Microarray analyses of the dorsal root ganglia support a role for innate neuro-immune pathways in persistent pain in experimental osteoarthritis
Following destabilization of the medial meniscus (DMM), mice develop experimental osteoarthritis (OA) and associated pain behaviors that are dependent on the stage of disease. We aimed to describe changes in gene expression in knee-innervating dorsal root ganglia (DRG) after surgery, in order to ide...
Gespeichert in:
| Veröffentlicht in: | Osteoarthritis and cartilage 2020-05, Vol.28 (5), p.581-592 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 592 |
|---|---|
| container_issue | 5 |
| container_start_page | 581 |
| container_title | Osteoarthritis and cartilage |
| container_volume | 28 |
| creator | Miller, R.E. Tran, P.B. Ishihara, S. Syx, D. Ren, D. Miller, R.J. Valdes, A.M. Malfait, A.M. |
| description | Following destabilization of the medial meniscus (DMM), mice develop experimental osteoarthritis (OA) and associated pain behaviors that are dependent on the stage of disease. We aimed to describe changes in gene expression in knee-innervating dorsal root ganglia (DRG) after surgery, in order to identify molecular pathways associated with three pre-defined pain phenotypes: “post-surgical pain”, “early-stage OA pain”, and “persistent OA pain”.
We performed DMM or sham surgery in 10-week old male C57BL/6 mice and harvested L3-L5 DRG 4, 8, and 16 weeks after surgery or from age-matched naïve mice (n = 3/group). RNA was extracted and an Affymetrix Mouse Transcriptome Array 1.0 was performed. Three pain phenotypes were defined: “post-surgical pain” (sham and DMM 4-week vs 14-week old naïve), “early OA pain” (DMM 4-week vs sham 4-week), and “persistent OA pain” (DMM 8- and 16-week vs naïve and sham 8- and 16-week). ‘Top hit’ genes were defined as P |
| doi_str_mv | 10.1016/j.joca.2020.01.008 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7214125</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1063458420300339</els_id><sourcerecordid>2346295928</sourcerecordid><originalsourceid>FETCH-LOGICAL-c455t-f7317532080487f7c05486e84a3384f41ba8f7288fd75228b7454b846871f6ec3</originalsourceid><addsrcrecordid>eNp9UU2LFDEQbURx19U_4EFy9NJtPrszIIIsfsGKFz2HTLoyk6E7aZP06vwLf7I1zLroRQgk9erVy6Ne0zxntGOU9a8O3SE523HKaUdZR6l-0FwyxXm76ZV4iG_ai1YqLS-aJ6UcKKWCMfq4uRBso7nq5WXz63NwOdmc7ZHYaKdjgUKSJ3UPZEy52InklCrZ2bibgiVlXZaUK7EIT0B8yiTEaCuQCGtObZjnNQJZbN3_sMeCTbJALqFUiBVhrPHATwTDjBDqJ-yhg7rPoYbytHnk7VTg2d191Xx7_-7r9cf25suHT9dvb1onlaqtHwQblOBUU6kHPziqpO5BSyuEll6yrdV-4Fr7ccCN6O0gldxq2euB-R6cuGrenHWXdTvD6NBLtpNZ0JbNR5NsMP92YtibXbo1A2eScYUCL-8Ecvq-QqlmDsXBNNkIaS2GC9nzjdpwjVR-puKqS8ng779h1JyiNAdzitKcojSUGYwSh178bfB-5E92SHh9JgCu6TZANsUFiA7GkMFVM6bwP_3fteOzuQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2346295928</pqid></control><display><type>article</type><title>Microarray analyses of the dorsal root ganglia support a role for innate neuro-immune pathways in persistent pain in experimental osteoarthritis</title><source>ScienceDirect Journals (5 years ago - present)</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Miller, R.E. ; Tran, P.B. ; Ishihara, S. ; Syx, D. ; Ren, D. ; Miller, R.J. ; Valdes, A.M. ; Malfait, A.M.</creator><creatorcontrib>Miller, R.E. ; Tran, P.B. ; Ishihara, S. ; Syx, D. ; Ren, D. ; Miller, R.J. ; Valdes, A.M. ; Malfait, A.M.</creatorcontrib><description>Following destabilization of the medial meniscus (DMM), mice develop experimental osteoarthritis (OA) and associated pain behaviors that are dependent on the stage of disease. We aimed to describe changes in gene expression in knee-innervating dorsal root ganglia (DRG) after surgery, in order to identify molecular pathways associated with three pre-defined pain phenotypes: “post-surgical pain”, “early-stage OA pain”, and “persistent OA pain”.
We performed DMM or sham surgery in 10-week old male C57BL/6 mice and harvested L3-L5 DRG 4, 8, and 16 weeks after surgery or from age-matched naïve mice (n = 3/group). RNA was extracted and an Affymetrix Mouse Transcriptome Array 1.0 was performed. Three pain phenotypes were defined: “post-surgical pain” (sham and DMM 4-week vs 14-week old naïve), “early OA pain” (DMM 4-week vs sham 4-week), and “persistent OA pain” (DMM 8- and 16-week vs naïve and sham 8- and 16-week). ‘Top hit’ genes were defined as P < 0.001. Pathway analysis (Ingenuity Pathway Analysis) was conducted using differentially expressed genes defined as P < 0.05. In addition, we performed qPCR for Ngf and immunohistochemistry for F4/80+ macrophages in the DRG.
For each phenotype, top hit genes identified a small number of differentially expressed genes, some of which have been previously associated with pain (7/67 for “post-surgical pain”; 2/14 for “early OA pain”; 8/37 for “persistent OA pain”). Overlap between groups was limited, with 8 genes differentially regulated (P < 0.05) in all three phenotypes. Pathway analysis showed that in the persistent OA pain phase many of the functions of differentially regulated genes are related to immune cell recruitment and activation. Genes previously linked to OA pain (CX3CL1, CCL2, TLR1, and NGF) were upregulated in this phenotype and contributed to activation of the neuroinflammation canonical pathway. In separate sets of mice, we confirmed that Ngf was elevated in the DRG 8 weeks after DMM (P = 0.03), and numbers of F4/80+ macrophages were increased 16 weeks after DMM (P = 0.002 vs Sham).
These transcriptomics findings support the idea that distinct molecular pathways discriminate early from persistent OA pain. Pathway analysis suggests neuroimmune interactions in the DRG contribute to initiation and maintenance of pain in OA.</description><identifier>ISSN: 1063-4584</identifier><identifier>EISSN: 1522-9653</identifier><identifier>DOI: 10.1016/j.joca.2020.01.008</identifier><identifier>PMID: 31982564</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Innate immunity ; Neuroinflammation ; Osteoarthritis ; Pain ; Sensitization ; Toll-like receptor</subject><ispartof>Osteoarthritis and cartilage, 2020-05, Vol.28 (5), p.581-592</ispartof><rights>2020 Osteoarthritis Research Society International</rights><rights>Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-f7317532080487f7c05486e84a3384f41ba8f7288fd75228b7454b846871f6ec3</citedby><cites>FETCH-LOGICAL-c455t-f7317532080487f7c05486e84a3384f41ba8f7288fd75228b7454b846871f6ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.joca.2020.01.008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31982564$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miller, R.E.</creatorcontrib><creatorcontrib>Tran, P.B.</creatorcontrib><creatorcontrib>Ishihara, S.</creatorcontrib><creatorcontrib>Syx, D.</creatorcontrib><creatorcontrib>Ren, D.</creatorcontrib><creatorcontrib>Miller, R.J.</creatorcontrib><creatorcontrib>Valdes, A.M.</creatorcontrib><creatorcontrib>Malfait, A.M.</creatorcontrib><title>Microarray analyses of the dorsal root ganglia support a role for innate neuro-immune pathways in persistent pain in experimental osteoarthritis</title><title>Osteoarthritis and cartilage</title><addtitle>Osteoarthritis Cartilage</addtitle><description>Following destabilization of the medial meniscus (DMM), mice develop experimental osteoarthritis (OA) and associated pain behaviors that are dependent on the stage of disease. We aimed to describe changes in gene expression in knee-innervating dorsal root ganglia (DRG) after surgery, in order to identify molecular pathways associated with three pre-defined pain phenotypes: “post-surgical pain”, “early-stage OA pain”, and “persistent OA pain”.
We performed DMM or sham surgery in 10-week old male C57BL/6 mice and harvested L3-L5 DRG 4, 8, and 16 weeks after surgery or from age-matched naïve mice (n = 3/group). RNA was extracted and an Affymetrix Mouse Transcriptome Array 1.0 was performed. Three pain phenotypes were defined: “post-surgical pain” (sham and DMM 4-week vs 14-week old naïve), “early OA pain” (DMM 4-week vs sham 4-week), and “persistent OA pain” (DMM 8- and 16-week vs naïve and sham 8- and 16-week). ‘Top hit’ genes were defined as P < 0.001. Pathway analysis (Ingenuity Pathway Analysis) was conducted using differentially expressed genes defined as P < 0.05. In addition, we performed qPCR for Ngf and immunohistochemistry for F4/80+ macrophages in the DRG.
For each phenotype, top hit genes identified a small number of differentially expressed genes, some of which have been previously associated with pain (7/67 for “post-surgical pain”; 2/14 for “early OA pain”; 8/37 for “persistent OA pain”). Overlap between groups was limited, with 8 genes differentially regulated (P < 0.05) in all three phenotypes. Pathway analysis showed that in the persistent OA pain phase many of the functions of differentially regulated genes are related to immune cell recruitment and activation. Genes previously linked to OA pain (CX3CL1, CCL2, TLR1, and NGF) were upregulated in this phenotype and contributed to activation of the neuroinflammation canonical pathway. In separate sets of mice, we confirmed that Ngf was elevated in the DRG 8 weeks after DMM (P = 0.03), and numbers of F4/80+ macrophages were increased 16 weeks after DMM (P = 0.002 vs Sham).
These transcriptomics findings support the idea that distinct molecular pathways discriminate early from persistent OA pain. Pathway analysis suggests neuroimmune interactions in the DRG contribute to initiation and maintenance of pain in OA.</description><subject>Innate immunity</subject><subject>Neuroinflammation</subject><subject>Osteoarthritis</subject><subject>Pain</subject><subject>Sensitization</subject><subject>Toll-like receptor</subject><issn>1063-4584</issn><issn>1522-9653</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9UU2LFDEQbURx19U_4EFy9NJtPrszIIIsfsGKFz2HTLoyk6E7aZP06vwLf7I1zLroRQgk9erVy6Ne0zxntGOU9a8O3SE523HKaUdZR6l-0FwyxXm76ZV4iG_ai1YqLS-aJ6UcKKWCMfq4uRBso7nq5WXz63NwOdmc7ZHYaKdjgUKSJ3UPZEy52InklCrZ2bibgiVlXZaUK7EIT0B8yiTEaCuQCGtObZjnNQJZbN3_sMeCTbJALqFUiBVhrPHATwTDjBDqJ-yhg7rPoYbytHnk7VTg2d191Xx7_-7r9cf25suHT9dvb1onlaqtHwQblOBUU6kHPziqpO5BSyuEll6yrdV-4Fr7ccCN6O0gldxq2euB-R6cuGrenHWXdTvD6NBLtpNZ0JbNR5NsMP92YtibXbo1A2eScYUCL-8Ecvq-QqlmDsXBNNkIaS2GC9nzjdpwjVR-puKqS8ng779h1JyiNAdzitKcojSUGYwSh178bfB-5E92SHh9JgCu6TZANsUFiA7GkMFVM6bwP_3fteOzuQ</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Miller, R.E.</creator><creator>Tran, P.B.</creator><creator>Ishihara, S.</creator><creator>Syx, D.</creator><creator>Ren, D.</creator><creator>Miller, R.J.</creator><creator>Valdes, A.M.</creator><creator>Malfait, A.M.</creator><general>Elsevier Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200501</creationdate><title>Microarray analyses of the dorsal root ganglia support a role for innate neuro-immune pathways in persistent pain in experimental osteoarthritis</title><author>Miller, R.E. ; Tran, P.B. ; Ishihara, S. ; Syx, D. ; Ren, D. ; Miller, R.J. ; Valdes, A.M. ; Malfait, A.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-f7317532080487f7c05486e84a3384f41ba8f7288fd75228b7454b846871f6ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Innate immunity</topic><topic>Neuroinflammation</topic><topic>Osteoarthritis</topic><topic>Pain</topic><topic>Sensitization</topic><topic>Toll-like receptor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miller, R.E.</creatorcontrib><creatorcontrib>Tran, P.B.</creatorcontrib><creatorcontrib>Ishihara, S.</creatorcontrib><creatorcontrib>Syx, D.</creatorcontrib><creatorcontrib>Ren, D.</creatorcontrib><creatorcontrib>Miller, R.J.</creatorcontrib><creatorcontrib>Valdes, A.M.</creatorcontrib><creatorcontrib>Malfait, A.M.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Osteoarthritis and cartilage</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miller, R.E.</au><au>Tran, P.B.</au><au>Ishihara, S.</au><au>Syx, D.</au><au>Ren, D.</au><au>Miller, R.J.</au><au>Valdes, A.M.</au><au>Malfait, A.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microarray analyses of the dorsal root ganglia support a role for innate neuro-immune pathways in persistent pain in experimental osteoarthritis</atitle><jtitle>Osteoarthritis and cartilage</jtitle><addtitle>Osteoarthritis Cartilage</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>28</volume><issue>5</issue><spage>581</spage><epage>592</epage><pages>581-592</pages><issn>1063-4584</issn><eissn>1522-9653</eissn><abstract>Following destabilization of the medial meniscus (DMM), mice develop experimental osteoarthritis (OA) and associated pain behaviors that are dependent on the stage of disease. We aimed to describe changes in gene expression in knee-innervating dorsal root ganglia (DRG) after surgery, in order to identify molecular pathways associated with three pre-defined pain phenotypes: “post-surgical pain”, “early-stage OA pain”, and “persistent OA pain”.
We performed DMM or sham surgery in 10-week old male C57BL/6 mice and harvested L3-L5 DRG 4, 8, and 16 weeks after surgery or from age-matched naïve mice (n = 3/group). RNA was extracted and an Affymetrix Mouse Transcriptome Array 1.0 was performed. Three pain phenotypes were defined: “post-surgical pain” (sham and DMM 4-week vs 14-week old naïve), “early OA pain” (DMM 4-week vs sham 4-week), and “persistent OA pain” (DMM 8- and 16-week vs naïve and sham 8- and 16-week). ‘Top hit’ genes were defined as P < 0.001. Pathway analysis (Ingenuity Pathway Analysis) was conducted using differentially expressed genes defined as P < 0.05. In addition, we performed qPCR for Ngf and immunohistochemistry for F4/80+ macrophages in the DRG.
For each phenotype, top hit genes identified a small number of differentially expressed genes, some of which have been previously associated with pain (7/67 for “post-surgical pain”; 2/14 for “early OA pain”; 8/37 for “persistent OA pain”). Overlap between groups was limited, with 8 genes differentially regulated (P < 0.05) in all three phenotypes. Pathway analysis showed that in the persistent OA pain phase many of the functions of differentially regulated genes are related to immune cell recruitment and activation. Genes previously linked to OA pain (CX3CL1, CCL2, TLR1, and NGF) were upregulated in this phenotype and contributed to activation of the neuroinflammation canonical pathway. In separate sets of mice, we confirmed that Ngf was elevated in the DRG 8 weeks after DMM (P = 0.03), and numbers of F4/80+ macrophages were increased 16 weeks after DMM (P = 0.002 vs Sham).
These transcriptomics findings support the idea that distinct molecular pathways discriminate early from persistent OA pain. Pathway analysis suggests neuroimmune interactions in the DRG contribute to initiation and maintenance of pain in OA.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>31982564</pmid><doi>10.1016/j.joca.2020.01.008</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1063-4584 |
| ispartof | Osteoarthritis and cartilage, 2020-05, Vol.28 (5), p.581-592 |
| issn | 1063-4584 1522-9653 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7214125 |
| source | ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals |
| subjects | Innate immunity Neuroinflammation Osteoarthritis Pain Sensitization Toll-like receptor |
| title | Microarray analyses of the dorsal root ganglia support a role for innate neuro-immune pathways in persistent pain in experimental osteoarthritis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T10%3A34%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Microarray%20analyses%20of%20the%20dorsal%20root%20ganglia%20support%20a%20role%20for%20innate%20neuro-immune%20pathways%20in%20persistent%20pain%20in%20experimental%20osteoarthritis&rft.jtitle=Osteoarthritis%20and%20cartilage&rft.au=Miller,%20R.E.&rft.date=2020-05-01&rft.volume=28&rft.issue=5&rft.spage=581&rft.epage=592&rft.pages=581-592&rft.issn=1063-4584&rft.eissn=1522-9653&rft_id=info:doi/10.1016/j.joca.2020.01.008&rft_dat=%3Cproquest_pubme%3E2346295928%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2346295928&rft_id=info:pmid/31982564&rft_els_id=S1063458420300339&rfr_iscdi=true |