ICOS-Ligand Triggering Impairs Osteoclast Differentiation and Function In Vitro and In Vivo
Osteoblasts, osteocytes, and osteoclasts (OCs) are involved in the bone production and resorption, which are crucial in bone homeostasis. OC hyperactivation plays a role in the exaggerated bone resorption of diseases such as osteoporosis, rheumatoid arthritis, and osteolytic tumor metastases. This w...
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| Veröffentlicht in: | The Journal of immunology (1950) 2016-11, Vol.197 (10), p.3905-3916 |
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| creator | Gigliotti, Casimiro L Boggio, Elena Clemente, Nausicaa Shivakumar, Yogesh Toth, Erika Sblattero, Daniele D'Amelio, Patrizia Isaia, Giovanni C Dianzani, Chiara Yagi, Junji Rojo, Josè M Chiocchetti, Annalisa Boldorini, Renzo Bosetti, Michela Dianzani, Umberto |
| description | Osteoblasts, osteocytes, and osteoclasts (OCs) are involved in the bone production and resorption, which are crucial in bone homeostasis. OC hyperactivation plays a role in the exaggerated bone resorption of diseases such as osteoporosis, rheumatoid arthritis, and osteolytic tumor metastases. This work stems from the finding that OCs can express B7h (ICOS-Ligand), which is the ligand of the ICOS T cell costimulatory molecule. Because recent reports have shown that, in endothelial, dendritic, and tumor cells, B7h triggering modulates several activities of these cells, we analyzed the effect of B7h triggering by recombinant ICOS-Fc on OC differentiation and function. The results showed that ICOS-Fc inhibits RANKL-mediated differentiation of human monocyte-derived OC-like cells (MDOCs) by inhibiting the acquirement of the OC morphology, the CD14
cathepsin K
phenotype, and the expression of tartrate-resistant acid phosphatase, OSCAR, NFATc1, and DC-STAMP. Moreover, ICOS-Fc induces a reversible decrease in the sizes of cells and nuclei and cathepsin K expression in mature MDOCs. Finally, ICOS-Fc inhibits the osteolytic activities of MDOCs in vitro and the development of bone loss in ovariectomized or soluble RANKL-treated mice. These findings open a novel field in the pharmacological use of agonists and antagonists of the ICOS-B7h system. |
| doi_str_mv | 10.4049/jimmunol.1600424 |
| format | Article |
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cathepsin K
phenotype, and the expression of tartrate-resistant acid phosphatase, OSCAR, NFATc1, and DC-STAMP. Moreover, ICOS-Fc induces a reversible decrease in the sizes of cells and nuclei and cathepsin K expression in mature MDOCs. Finally, ICOS-Fc inhibits the osteolytic activities of MDOCs in vitro and the development of bone loss in ovariectomized or soluble RANKL-treated mice. These findings open a novel field in the pharmacological use of agonists and antagonists of the ICOS-B7h system.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1600424</identifier><identifier>PMID: 27798154</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Cell Differentiation ; Cell Movement ; Cells, Cultured ; Humans ; Inducible T-Cell Co-Stimulator Ligand - genetics ; Inducible T-Cell Co-Stimulator Ligand - immunology ; Inducible T-Cell Co-Stimulator Ligand - metabolism ; Inducible T-Cell Co-Stimulator Ligand - pharmacology ; Inducible T-Cell Co-Stimulator Protein - genetics ; Inducible T-Cell Co-Stimulator Protein - metabolism ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Mice ; Monocytes - immunology ; Monocytes - physiology ; Osteoclasts - drug effects ; Osteoclasts - immunology ; Osteoclasts - physiology ; Protein Engineering ; RANK Ligand - antagonists & inhibitors ; RANK Ligand - metabolism ; Receptor Activator of Nuclear Factor-kappa B - metabolism ; Receptors, Fc - genetics ; Receptors, Fc - immunology ; Recombinant Fusion Proteins - pharmacology ; Tartrate-Resistant Acid Phosphatase - immunology</subject><ispartof>The Journal of immunology (1950), 2016-11, Vol.197 (10), p.3905-3916</ispartof><rights>Copyright © 2016 by The American Association of Immunologists, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c374t-f38a3fe0ba5d15886d07a096cc66cf201f6698866adec9f27ae0013a60b0b50a3</citedby><cites>FETCH-LOGICAL-c374t-f38a3fe0ba5d15886d07a096cc66cf201f6698866adec9f27ae0013a60b0b50a3</cites><orcidid>0000-0003-2669-6328 ; 0000-0002-9860-0148 ; 0000-0003-4309-242X ; 0000-0003-2700-3597 ; 0000-0001-9032-0072 ; 0000-0002-3682-8702 ; 0000-0002-3127-5686</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27798154$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gigliotti, Casimiro L</creatorcontrib><creatorcontrib>Boggio, Elena</creatorcontrib><creatorcontrib>Clemente, Nausicaa</creatorcontrib><creatorcontrib>Shivakumar, Yogesh</creatorcontrib><creatorcontrib>Toth, Erika</creatorcontrib><creatorcontrib>Sblattero, Daniele</creatorcontrib><creatorcontrib>D'Amelio, Patrizia</creatorcontrib><creatorcontrib>Isaia, Giovanni C</creatorcontrib><creatorcontrib>Dianzani, Chiara</creatorcontrib><creatorcontrib>Yagi, Junji</creatorcontrib><creatorcontrib>Rojo, Josè M</creatorcontrib><creatorcontrib>Chiocchetti, Annalisa</creatorcontrib><creatorcontrib>Boldorini, Renzo</creatorcontrib><creatorcontrib>Bosetti, Michela</creatorcontrib><creatorcontrib>Dianzani, Umberto</creatorcontrib><title>ICOS-Ligand Triggering Impairs Osteoclast Differentiation and Function In Vitro and In Vivo</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Osteoblasts, osteocytes, and osteoclasts (OCs) are involved in the bone production and resorption, which are crucial in bone homeostasis. OC hyperactivation plays a role in the exaggerated bone resorption of diseases such as osteoporosis, rheumatoid arthritis, and osteolytic tumor metastases. This work stems from the finding that OCs can express B7h (ICOS-Ligand), which is the ligand of the ICOS T cell costimulatory molecule. Because recent reports have shown that, in endothelial, dendritic, and tumor cells, B7h triggering modulates several activities of these cells, we analyzed the effect of B7h triggering by recombinant ICOS-Fc on OC differentiation and function. The results showed that ICOS-Fc inhibits RANKL-mediated differentiation of human monocyte-derived OC-like cells (MDOCs) by inhibiting the acquirement of the OC morphology, the CD14
cathepsin K
phenotype, and the expression of tartrate-resistant acid phosphatase, OSCAR, NFATc1, and DC-STAMP. Moreover, ICOS-Fc induces a reversible decrease in the sizes of cells and nuclei and cathepsin K expression in mature MDOCs. Finally, ICOS-Fc inhibits the osteolytic activities of MDOCs in vitro and the development of bone loss in ovariectomized or soluble RANKL-treated mice. These findings open a novel field in the pharmacological use of agonists and antagonists of the ICOS-B7h system.</description><subject>Animals</subject><subject>Cell Differentiation</subject><subject>Cell Movement</subject><subject>Cells, Cultured</subject><subject>Humans</subject><subject>Inducible T-Cell Co-Stimulator Ligand - genetics</subject><subject>Inducible T-Cell Co-Stimulator Ligand - immunology</subject><subject>Inducible T-Cell Co-Stimulator Ligand - metabolism</subject><subject>Inducible T-Cell Co-Stimulator Ligand - pharmacology</subject><subject>Inducible T-Cell Co-Stimulator Protein - genetics</subject><subject>Inducible T-Cell Co-Stimulator Protein - metabolism</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mice</subject><subject>Monocytes - immunology</subject><subject>Monocytes - physiology</subject><subject>Osteoclasts - drug effects</subject><subject>Osteoclasts - immunology</subject><subject>Osteoclasts - physiology</subject><subject>Protein Engineering</subject><subject>RANK Ligand - antagonists & inhibitors</subject><subject>RANK Ligand - metabolism</subject><subject>Receptor Activator of Nuclear Factor-kappa B - metabolism</subject><subject>Receptors, Fc - genetics</subject><subject>Receptors, Fc - immunology</subject><subject>Recombinant Fusion Proteins - pharmacology</subject><subject>Tartrate-Resistant Acid Phosphatase - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkD1PwzAYhC0EoqWwM6GMLCmvP-LEIyoUIlXqQGFhiBzHjlwlTrETJP49_WRmOt3p7oYHoVsMUwZMPKxt2w6ua6aYAzDCztAYJwnEnAM_R2MAQmKc8nSErkJYAwAHwi7RiKSpyHDCxugzny3f4oWtpauilbd1rb11dZS3G2l9iJah151qZOijJ2uM9tr1Vva2c9FuMR-c2pvcRR-2990-3Zvv7hpdGNkEfXPUCXqfP69mr_Fi-ZLPHhexoinrY0MzSY2GUiYVTrKMV5BKEFwpzpUhgA3nYhtzWWklDEmlBsBUciihTEDSCbo__G589zXo0BetDUo3jXS6G0KBM8apEATzf1QpEyJLALZVOFSV70Lw2hQbb1vpfwoMxY5-caJfHOlvJ3fH96FsdfU3OOGmv5MlgaQ</recordid><startdate>20161115</startdate><enddate>20161115</enddate><creator>Gigliotti, Casimiro L</creator><creator>Boggio, Elena</creator><creator>Clemente, Nausicaa</creator><creator>Shivakumar, Yogesh</creator><creator>Toth, Erika</creator><creator>Sblattero, Daniele</creator><creator>D'Amelio, Patrizia</creator><creator>Isaia, Giovanni C</creator><creator>Dianzani, Chiara</creator><creator>Yagi, Junji</creator><creator>Rojo, Josè M</creator><creator>Chiocchetti, Annalisa</creator><creator>Boldorini, Renzo</creator><creator>Bosetti, Michela</creator><creator>Dianzani, Umberto</creator><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>7X8</scope><scope>7QP</scope><scope>7T5</scope><scope>H94</scope><orcidid>https://orcid.org/0000-0003-2669-6328</orcidid><orcidid>https://orcid.org/0000-0002-9860-0148</orcidid><orcidid>https://orcid.org/0000-0003-4309-242X</orcidid><orcidid>https://orcid.org/0000-0003-2700-3597</orcidid><orcidid>https://orcid.org/0000-0001-9032-0072</orcidid><orcidid>https://orcid.org/0000-0002-3682-8702</orcidid><orcidid>https://orcid.org/0000-0002-3127-5686</orcidid></search><sort><creationdate>20161115</creationdate><title>ICOS-Ligand Triggering Impairs Osteoclast Differentiation and Function In Vitro and In Vivo</title><author>Gigliotti, Casimiro L ; Boggio, Elena ; Clemente, Nausicaa ; Shivakumar, Yogesh ; Toth, Erika ; Sblattero, Daniele ; D'Amelio, Patrizia ; Isaia, Giovanni C ; Dianzani, Chiara ; Yagi, Junji ; Rojo, Josè M ; Chiocchetti, Annalisa ; Boldorini, Renzo ; Bosetti, Michela ; Dianzani, Umberto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c374t-f38a3fe0ba5d15886d07a096cc66cf201f6698866adec9f27ae0013a60b0b50a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Cell Differentiation</topic><topic>Cell Movement</topic><topic>Cells, Cultured</topic><topic>Humans</topic><topic>Inducible T-Cell Co-Stimulator Ligand - genetics</topic><topic>Inducible T-Cell Co-Stimulator Ligand - immunology</topic><topic>Inducible T-Cell Co-Stimulator Ligand - metabolism</topic><topic>Inducible T-Cell Co-Stimulator Ligand - pharmacology</topic><topic>Inducible T-Cell Co-Stimulator Protein - genetics</topic><topic>Inducible T-Cell Co-Stimulator Protein - metabolism</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mice</topic><topic>Monocytes - immunology</topic><topic>Monocytes - physiology</topic><topic>Osteoclasts - drug effects</topic><topic>Osteoclasts - immunology</topic><topic>Osteoclasts - physiology</topic><topic>Protein Engineering</topic><topic>RANK Ligand - antagonists & inhibitors</topic><topic>RANK Ligand - metabolism</topic><topic>Receptor Activator of Nuclear Factor-kappa B - metabolism</topic><topic>Receptors, Fc - genetics</topic><topic>Receptors, Fc - immunology</topic><topic>Recombinant Fusion Proteins - pharmacology</topic><topic>Tartrate-Resistant Acid Phosphatase - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gigliotti, Casimiro L</creatorcontrib><creatorcontrib>Boggio, Elena</creatorcontrib><creatorcontrib>Clemente, Nausicaa</creatorcontrib><creatorcontrib>Shivakumar, Yogesh</creatorcontrib><creatorcontrib>Toth, Erika</creatorcontrib><creatorcontrib>Sblattero, Daniele</creatorcontrib><creatorcontrib>D'Amelio, Patrizia</creatorcontrib><creatorcontrib>Isaia, Giovanni C</creatorcontrib><creatorcontrib>Dianzani, Chiara</creatorcontrib><creatorcontrib>Yagi, Junji</creatorcontrib><creatorcontrib>Rojo, Josè M</creatorcontrib><creatorcontrib>Chiocchetti, Annalisa</creatorcontrib><creatorcontrib>Boldorini, Renzo</creatorcontrib><creatorcontrib>Bosetti, Michela</creatorcontrib><creatorcontrib>Dianzani, Umberto</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gigliotti, Casimiro L</au><au>Boggio, Elena</au><au>Clemente, Nausicaa</au><au>Shivakumar, Yogesh</au><au>Toth, Erika</au><au>Sblattero, Daniele</au><au>D'Amelio, Patrizia</au><au>Isaia, Giovanni C</au><au>Dianzani, Chiara</au><au>Yagi, Junji</au><au>Rojo, Josè M</au><au>Chiocchetti, Annalisa</au><au>Boldorini, Renzo</au><au>Bosetti, Michela</au><au>Dianzani, Umberto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ICOS-Ligand Triggering Impairs Osteoclast Differentiation and Function In Vitro and In Vivo</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2016-11-15</date><risdate>2016</risdate><volume>197</volume><issue>10</issue><spage>3905</spage><epage>3916</epage><pages>3905-3916</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Osteoblasts, osteocytes, and osteoclasts (OCs) are involved in the bone production and resorption, which are crucial in bone homeostasis. OC hyperactivation plays a role in the exaggerated bone resorption of diseases such as osteoporosis, rheumatoid arthritis, and osteolytic tumor metastases. This work stems from the finding that OCs can express B7h (ICOS-Ligand), which is the ligand of the ICOS T cell costimulatory molecule. Because recent reports have shown that, in endothelial, dendritic, and tumor cells, B7h triggering modulates several activities of these cells, we analyzed the effect of B7h triggering by recombinant ICOS-Fc on OC differentiation and function. The results showed that ICOS-Fc inhibits RANKL-mediated differentiation of human monocyte-derived OC-like cells (MDOCs) by inhibiting the acquirement of the OC morphology, the CD14
cathepsin K
phenotype, and the expression of tartrate-resistant acid phosphatase, OSCAR, NFATc1, and DC-STAMP. Moreover, ICOS-Fc induces a reversible decrease in the sizes of cells and nuclei and cathepsin K expression in mature MDOCs. Finally, ICOS-Fc inhibits the osteolytic activities of MDOCs in vitro and the development of bone loss in ovariectomized or soluble RANKL-treated mice. These findings open a novel field in the pharmacological use of agonists and antagonists of the ICOS-B7h system.</abstract><cop>United States</cop><pmid>27798154</pmid><doi>10.4049/jimmunol.1600424</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-2669-6328</orcidid><orcidid>https://orcid.org/0000-0002-9860-0148</orcidid><orcidid>https://orcid.org/0000-0003-4309-242X</orcidid><orcidid>https://orcid.org/0000-0003-2700-3597</orcidid><orcidid>https://orcid.org/0000-0001-9032-0072</orcidid><orcidid>https://orcid.org/0000-0002-3682-8702</orcidid><orcidid>https://orcid.org/0000-0002-3127-5686</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cell Differentiation Cell Movement Cells, Cultured Humans Inducible T-Cell Co-Stimulator Ligand - genetics Inducible T-Cell Co-Stimulator Ligand - immunology Inducible T-Cell Co-Stimulator Ligand - metabolism Inducible T-Cell Co-Stimulator Ligand - pharmacology Inducible T-Cell Co-Stimulator Protein - genetics Inducible T-Cell Co-Stimulator Protein - metabolism Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Mice Monocytes - immunology Monocytes - physiology Osteoclasts - drug effects Osteoclasts - immunology Osteoclasts - physiology Protein Engineering RANK Ligand - antagonists & inhibitors RANK Ligand - metabolism Receptor Activator of Nuclear Factor-kappa B - metabolism Receptors, Fc - genetics Receptors, Fc - immunology Recombinant Fusion Proteins - pharmacology Tartrate-Resistant Acid Phosphatase - immunology |
| title | ICOS-Ligand Triggering Impairs Osteoclast Differentiation and Function In Vitro and In Vivo |
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