RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation
ObjectiveRANKL is mainly expressed by synovial fibroblasts and T cells within the joints of rheumatoid arthritis patients. The relative importance of RANKL expression by these cell types for the formation of bone erosions is unclear. We therefore aimed to quantify the contribution of RANKL by each c...
Gespeichert in:
| Veröffentlicht in: | Annals of the rheumatic diseases 2016-06, Vol.75 (6), p.1187-1195 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1195 |
|---|---|
| container_issue | 6 |
| container_start_page | 1187 |
| container_title | Annals of the rheumatic diseases |
| container_volume | 75 |
| creator | Danks, Lynett Komatsu, Noriko Guerrini, Matteo M Sawa, Shinichiro Armaka, Marietta Kollias, George Nakashima, Tomoki Takayanagi, Hiroshi |
| description | ObjectiveRANKL is mainly expressed by synovial fibroblasts and T cells within the joints of rheumatoid arthritis patients. The relative importance of RANKL expression by these cell types for the formation of bone erosions is unclear. We therefore aimed to quantify the contribution of RANKL by each cell type to osteoclast differentiation and bone destruction during inflammatory arthritis.MethodsRANKL was specifically deleted in T cells (Tnfsf11flox/Δ Lck-Cre), in collagen VI expressing cells including synovial fibroblasts (Tnfsf11flox/Δ Col6a1-Cre) and in collagen II expressing cells including articular chondrocytes (Tnfsf11flox/Δ Col2a1-Cre). Erosive disease was induced using the collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA) models. Osteoclasts and cartilage degradation were assessed by histology and bone erosions were assessed by micro-CT.ResultsThe inflammatory joint score during CAIA was equivalent in all mice regardless of cell-targeted deletion of RANKL. Significant increases in osteoclast numbers and bone erosions were observed in both the Tnfsf11flox/Δ and the Tnfsf11flox/Δ Lck-Cre groups during CAIA; however, the Tnfsf11flox/Δ Col6a1-Cre mice showed significant protection against osteoclast formation and bone erosions. Similar results on osteoclast formation and bone erosions were obtained in CIA mice. The deletion of RANKL on any cell type did not prevent articular cartilage loss in either model of arthritis used.ConclusionsThe expression of RANKL on synovial fibroblasts rather than T cells is predominantly responsible for the formation of osteoclasts and erosions during inflammatory arthritis. Synovial fibroblasts would be the best direct target in RANKL inhibition therapies. |
| doi_str_mv | 10.1136/annrheumdis-2014-207137 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1788537223</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1788537223</sourcerecordid><originalsourceid>FETCH-LOGICAL-b450t-216d44a8c6ec973de9835f346f029c9ade192a5286977085293cb0835a87e67e3</originalsourceid><addsrcrecordid>eNqNkUtP3DAURq0K1Bmm_QvFEptuAn4kfixHiAJiRCVE15GT3BSPHHuwk4r59zXKFCFW3di69rmfrn0QOqXknFIuLoz38QmmobOpYISWeZGUy09oSUuhciXIEVoSQnhRaiEX6CSlbS6JouozWjBBWKUlXSL3sL6_22B42UVICTocPE57H_5Y43BvmxgaZ9KYsE14F-1gonV7nNld8Mk2DnAfIm6CBwwxJJtPcTdF63_jbbB-xNb3zgyDGfPVF3TcG5fg62FfoV8_rh4vb4rNz-vby_WmaMqKjAWjoitLo1oBrZa8A6141fNS9ITpVpsOqGamYkpoKYmqmOZtQzJjlAQhga_Q9zl3F8PzBGmsB5tacM54CFOqqVSq4pIxntGzD-g2TNHn6TKluWKVVCJTcqba_MYUoa_nv9jXlNSvQup3QupXIfUsJHd-O-RPzQDdW98_AxlgM9AM2_9O_Qt36ZtY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1793825786</pqid></control><display><type>article</type><title>RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation</title><source>BMJ Journals Online Archive</source><source>MEDLINE</source><creator>Danks, Lynett ; Komatsu, Noriko ; Guerrini, Matteo M ; Sawa, Shinichiro ; Armaka, Marietta ; Kollias, George ; Nakashima, Tomoki ; Takayanagi, Hiroshi</creator><creatorcontrib>Danks, Lynett ; Komatsu, Noriko ; Guerrini, Matteo M ; Sawa, Shinichiro ; Armaka, Marietta ; Kollias, George ; Nakashima, Tomoki ; Takayanagi, Hiroshi</creatorcontrib><description>ObjectiveRANKL is mainly expressed by synovial fibroblasts and T cells within the joints of rheumatoid arthritis patients. The relative importance of RANKL expression by these cell types for the formation of bone erosions is unclear. We therefore aimed to quantify the contribution of RANKL by each cell type to osteoclast differentiation and bone destruction during inflammatory arthritis.MethodsRANKL was specifically deleted in T cells (Tnfsf11flox/Δ Lck-Cre), in collagen VI expressing cells including synovial fibroblasts (Tnfsf11flox/Δ Col6a1-Cre) and in collagen II expressing cells including articular chondrocytes (Tnfsf11flox/Δ Col2a1-Cre). Erosive disease was induced using the collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA) models. Osteoclasts and cartilage degradation were assessed by histology and bone erosions were assessed by micro-CT.ResultsThe inflammatory joint score during CAIA was equivalent in all mice regardless of cell-targeted deletion of RANKL. Significant increases in osteoclast numbers and bone erosions were observed in both the Tnfsf11flox/Δ and the Tnfsf11flox/Δ Lck-Cre groups during CAIA; however, the Tnfsf11flox/Δ Col6a1-Cre mice showed significant protection against osteoclast formation and bone erosions. Similar results on osteoclast formation and bone erosions were obtained in CIA mice. The deletion of RANKL on any cell type did not prevent articular cartilage loss in either model of arthritis used.ConclusionsThe expression of RANKL on synovial fibroblasts rather than T cells is predominantly responsible for the formation of osteoclasts and erosions during inflammatory arthritis. Synovial fibroblasts would be the best direct target in RANKL inhibition therapies.</description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/annrheumdis-2014-207137</identifier><identifier>PMID: 26025971</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>England: Elsevier Limited</publisher><subject>Animals ; Arthritis ; Arthritis, Experimental - immunology ; Arthritis, Experimental - metabolism ; Arthritis, Experimental - pathology ; Bone Remodeling - physiology ; Bone Resorption - etiology ; Bone Resorption - metabolism ; Bone Resorption - pathology ; Cartilage ; Cartilage, Articular - metabolism ; Cartilage, Articular - pathology ; CD4-Positive T-Lymphocytes - immunology ; Cell Differentiation ; Chondrocytes - metabolism ; Collagen ; Fibroblasts ; Fibroblasts - metabolism ; Gene Deletion ; Inflammation ; Knee ; Lymphocytes ; Male ; Mice, Inbred C57BL ; Osteoclasts - pathology ; Physiology ; RANK Ligand - genetics ; RANK Ligand - metabolism ; Synovial Membrane - metabolism</subject><ispartof>Annals of the rheumatic diseases, 2016-06, Vol.75 (6), p.1187-1195</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing</rights><rights>Copyright: 2016 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b450t-216d44a8c6ec973de9835f346f029c9ade192a5286977085293cb0835a87e67e3</citedby><cites>FETCH-LOGICAL-b450t-216d44a8c6ec973de9835f346f029c9ade192a5286977085293cb0835a87e67e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/75/6/1187.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/75/6/1187.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,776,780,3183,23550,27901,27902,77342,77373</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26025971$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Danks, Lynett</creatorcontrib><creatorcontrib>Komatsu, Noriko</creatorcontrib><creatorcontrib>Guerrini, Matteo M</creatorcontrib><creatorcontrib>Sawa, Shinichiro</creatorcontrib><creatorcontrib>Armaka, Marietta</creatorcontrib><creatorcontrib>Kollias, George</creatorcontrib><creatorcontrib>Nakashima, Tomoki</creatorcontrib><creatorcontrib>Takayanagi, Hiroshi</creatorcontrib><title>RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation</title><title>Annals of the rheumatic diseases</title><addtitle>Ann Rheum Dis</addtitle><description>ObjectiveRANKL is mainly expressed by synovial fibroblasts and T cells within the joints of rheumatoid arthritis patients. The relative importance of RANKL expression by these cell types for the formation of bone erosions is unclear. We therefore aimed to quantify the contribution of RANKL by each cell type to osteoclast differentiation and bone destruction during inflammatory arthritis.MethodsRANKL was specifically deleted in T cells (Tnfsf11flox/Δ Lck-Cre), in collagen VI expressing cells including synovial fibroblasts (Tnfsf11flox/Δ Col6a1-Cre) and in collagen II expressing cells including articular chondrocytes (Tnfsf11flox/Δ Col2a1-Cre). Erosive disease was induced using the collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA) models. Osteoclasts and cartilage degradation were assessed by histology and bone erosions were assessed by micro-CT.ResultsThe inflammatory joint score during CAIA was equivalent in all mice regardless of cell-targeted deletion of RANKL. Significant increases in osteoclast numbers and bone erosions were observed in both the Tnfsf11flox/Δ and the Tnfsf11flox/Δ Lck-Cre groups during CAIA; however, the Tnfsf11flox/Δ Col6a1-Cre mice showed significant protection against osteoclast formation and bone erosions. Similar results on osteoclast formation and bone erosions were obtained in CIA mice. The deletion of RANKL on any cell type did not prevent articular cartilage loss in either model of arthritis used.ConclusionsThe expression of RANKL on synovial fibroblasts rather than T cells is predominantly responsible for the formation of osteoclasts and erosions during inflammatory arthritis. Synovial fibroblasts would be the best direct target in RANKL inhibition therapies.</description><subject>Animals</subject><subject>Arthritis</subject><subject>Arthritis, Experimental - immunology</subject><subject>Arthritis, Experimental - metabolism</subject><subject>Arthritis, Experimental - pathology</subject><subject>Bone Remodeling - physiology</subject><subject>Bone Resorption - etiology</subject><subject>Bone Resorption - metabolism</subject><subject>Bone Resorption - pathology</subject><subject>Cartilage</subject><subject>Cartilage, Articular - metabolism</subject><subject>Cartilage, Articular - pathology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cell Differentiation</subject><subject>Chondrocytes - metabolism</subject><subject>Collagen</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Gene Deletion</subject><subject>Inflammation</subject><subject>Knee</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Osteoclasts - pathology</subject><subject>Physiology</subject><subject>RANK Ligand - genetics</subject><subject>RANK Ligand - metabolism</subject><subject>Synovial Membrane - metabolism</subject><issn>0003-4967</issn><issn>1468-2060</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkUtP3DAURq0K1Bmm_QvFEptuAn4kfixHiAJiRCVE15GT3BSPHHuwk4r59zXKFCFW3di69rmfrn0QOqXknFIuLoz38QmmobOpYISWeZGUy09oSUuhciXIEVoSQnhRaiEX6CSlbS6JouozWjBBWKUlXSL3sL6_22B42UVICTocPE57H_5Y43BvmxgaZ9KYsE14F-1gonV7nNld8Mk2DnAfIm6CBwwxJJtPcTdF63_jbbB-xNb3zgyDGfPVF3TcG5fg62FfoV8_rh4vb4rNz-vby_WmaMqKjAWjoitLo1oBrZa8A6141fNS9ITpVpsOqGamYkpoKYmqmOZtQzJjlAQhga_Q9zl3F8PzBGmsB5tacM54CFOqqVSq4pIxntGzD-g2TNHn6TKluWKVVCJTcqba_MYUoa_nv9jXlNSvQup3QupXIfUsJHd-O-RPzQDdW98_AxlgM9AM2_9O_Qt36ZtY</recordid><startdate>20160601</startdate><enddate>20160601</enddate><creator>Danks, Lynett</creator><creator>Komatsu, Noriko</creator><creator>Guerrini, Matteo M</creator><creator>Sawa, Shinichiro</creator><creator>Armaka, Marietta</creator><creator>Kollias, George</creator><creator>Nakashima, Tomoki</creator><creator>Takayanagi, Hiroshi</creator><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20160601</creationdate><title>RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation</title><author>Danks, Lynett ; Komatsu, Noriko ; Guerrini, Matteo M ; Sawa, Shinichiro ; Armaka, Marietta ; Kollias, George ; Nakashima, Tomoki ; Takayanagi, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b450t-216d44a8c6ec973de9835f346f029c9ade192a5286977085293cb0835a87e67e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Arthritis</topic><topic>Arthritis, Experimental - immunology</topic><topic>Arthritis, Experimental - metabolism</topic><topic>Arthritis, Experimental - pathology</topic><topic>Bone Remodeling - physiology</topic><topic>Bone Resorption - etiology</topic><topic>Bone Resorption - metabolism</topic><topic>Bone Resorption - pathology</topic><topic>Cartilage</topic><topic>Cartilage, Articular - metabolism</topic><topic>Cartilage, Articular - pathology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Cell Differentiation</topic><topic>Chondrocytes - metabolism</topic><topic>Collagen</topic><topic>Fibroblasts</topic><topic>Fibroblasts - metabolism</topic><topic>Gene Deletion</topic><topic>Inflammation</topic><topic>Knee</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Osteoclasts - pathology</topic><topic>Physiology</topic><topic>RANK Ligand - genetics</topic><topic>RANK Ligand - metabolism</topic><topic>Synovial Membrane - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Danks, Lynett</creatorcontrib><creatorcontrib>Komatsu, Noriko</creatorcontrib><creatorcontrib>Guerrini, Matteo M</creatorcontrib><creatorcontrib>Sawa, Shinichiro</creatorcontrib><creatorcontrib>Armaka, Marietta</creatorcontrib><creatorcontrib>Kollias, George</creatorcontrib><creatorcontrib>Nakashima, Tomoki</creatorcontrib><creatorcontrib>Takayanagi, Hiroshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Science Journals</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Danks, Lynett</au><au>Komatsu, Noriko</au><au>Guerrini, Matteo M</au><au>Sawa, Shinichiro</au><au>Armaka, Marietta</au><au>Kollias, George</au><au>Nakashima, Tomoki</au><au>Takayanagi, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation</atitle><jtitle>Annals of the rheumatic diseases</jtitle><addtitle>Ann Rheum Dis</addtitle><date>2016-06-01</date><risdate>2016</risdate><volume>75</volume><issue>6</issue><spage>1187</spage><epage>1195</epage><pages>1187-1195</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract>ObjectiveRANKL is mainly expressed by synovial fibroblasts and T cells within the joints of rheumatoid arthritis patients. The relative importance of RANKL expression by these cell types for the formation of bone erosions is unclear. We therefore aimed to quantify the contribution of RANKL by each cell type to osteoclast differentiation and bone destruction during inflammatory arthritis.MethodsRANKL was specifically deleted in T cells (Tnfsf11flox/Δ Lck-Cre), in collagen VI expressing cells including synovial fibroblasts (Tnfsf11flox/Δ Col6a1-Cre) and in collagen II expressing cells including articular chondrocytes (Tnfsf11flox/Δ Col2a1-Cre). Erosive disease was induced using the collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA) models. Osteoclasts and cartilage degradation were assessed by histology and bone erosions were assessed by micro-CT.ResultsThe inflammatory joint score during CAIA was equivalent in all mice regardless of cell-targeted deletion of RANKL. Significant increases in osteoclast numbers and bone erosions were observed in both the Tnfsf11flox/Δ and the Tnfsf11flox/Δ Lck-Cre groups during CAIA; however, the Tnfsf11flox/Δ Col6a1-Cre mice showed significant protection against osteoclast formation and bone erosions. Similar results on osteoclast formation and bone erosions were obtained in CIA mice. The deletion of RANKL on any cell type did not prevent articular cartilage loss in either model of arthritis used.ConclusionsThe expression of RANKL on synovial fibroblasts rather than T cells is predominantly responsible for the formation of osteoclasts and erosions during inflammatory arthritis. Synovial fibroblasts would be the best direct target in RANKL inhibition therapies.</abstract><cop>England</cop><pub>Elsevier Limited</pub><pmid>26025971</pmid><doi>10.1136/annrheumdis-2014-207137</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0003-4967 |
| ispartof | Annals of the rheumatic diseases, 2016-06, Vol.75 (6), p.1187-1195 |
| issn | 0003-4967 1468-2060 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1788537223 |
| source | BMJ Journals Online Archive; MEDLINE |
| subjects | Animals Arthritis Arthritis, Experimental - immunology Arthritis, Experimental - metabolism Arthritis, Experimental - pathology Bone Remodeling - physiology Bone Resorption - etiology Bone Resorption - metabolism Bone Resorption - pathology Cartilage Cartilage, Articular - metabolism Cartilage, Articular - pathology CD4-Positive T-Lymphocytes - immunology Cell Differentiation Chondrocytes - metabolism Collagen Fibroblasts Fibroblasts - metabolism Gene Deletion Inflammation Knee Lymphocytes Male Mice, Inbred C57BL Osteoclasts - pathology Physiology RANK Ligand - genetics RANK Ligand - metabolism Synovial Membrane - metabolism |
| title | RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T18%3A16%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=RANKL%20expressed%20on%20synovial%20fibroblasts%20is%20primarily%20responsible%20for%20bone%20erosions%20during%20joint%20inflammation&rft.jtitle=Annals%20of%20the%20rheumatic%20diseases&rft.au=Danks,%20Lynett&rft.date=2016-06-01&rft.volume=75&rft.issue=6&rft.spage=1187&rft.epage=1195&rft.pages=1187-1195&rft.issn=0003-4967&rft.eissn=1468-2060&rft.coden=ARDIAO&rft_id=info:doi/10.1136/annrheumdis-2014-207137&rft_dat=%3Cproquest_cross%3E1788537223%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1793825786&rft_id=info:pmid/26025971&rfr_iscdi=true |