{"id":5408,"date":"2019-11-19T09:56:57","date_gmt":"2019-11-19T00:56:57","guid":{"rendered":"http:\/\/www.med.osaka-u.ac.jp\/eng\/?page_id=5408"},"modified":"2022-08-26T14:57:19","modified_gmt":"2022-08-26T05:57:19","slug":"ishii201911","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2019year\/ishii201911","title":{"rendered":"Tetsuo Hasegawa, Masaru Ishii \u226aImmunology and Cell Biology\u226b <span>Researchers split the \u201cAtoM\u201d in search of a treatment for rheumatoid arthritis<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li><a href=\"http:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2019year\/ishii201911\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p>2019-11-19<br \/><em><em><\/p>\n<p><span class=\"lineFrame\">Publish\u00a0<\/span> <em>Nature Immunology<\/em><\/p>\n<p><em>Researchers at Osaka University discover a new type of bone-dissolving osteoclast that contributes to rheumatoid arthritis<\/em><\/p>\n<p class=\"figure\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-5417 size-medium\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/4c91d76fc4075d5b09d799ccb1e3fc4d-400x264.png?_t=1574298073\" alt=\"\" width=\"400\" height=\"264\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/4c91d76fc4075d5b09d799ccb1e3fc4d-400x264.png 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/4c91d76fc4075d5b09d799ccb1e3fc4d.png 632w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/><a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/4c91d76fc4075d5b09d799ccb1e3fc4d.png\"> <span class=\"caption\"><strong>Figure 1. Protocol for isolating joint tissue in arthritic mice<\/strong><br \/><strong>a<\/strong>, Schematic showing that hypertrophied joint tissue exists behind the knee ligament.<br \/><strong>b<\/strong>, Protocol for removing muscles and isolating joint tissue.<br \/><span class=\"click\">Click to enlarge<\/span><\/span><\/a><\/p>\n<p>Arthritis is a common chronic disease in which joints become inflamed, leading to stiffness and pain that can often be debilitating. Rheumatoid arthritis (RA) is an autoimmune form of the disease, arising when immune cells attack the tissue that lines the joints. There is a need for new treatment options, as current therapies only alleviate symptoms or, at best, slow the disease. Now, in a study published in <em>Nature Immunology<\/em>, researchers at Osaka University have discovered a previously unknown type of RA-causing cell within arthritic joints that could someday be a target for new treatments.<\/p>\n<p>There are two major cellular culprits that contribute to RA. The first are immune cells, which release inflammatory chemicals around the tissue of affected joints. The second are osteoclasts, specialized cells that secrete acids and enzymes to break down bone. Osteoclasts normally help to remodel healthy bone, but in RA their bone-dissolving ability goes into overdrive and damages joints.<\/p>\n<p>\u201cThe disease-modifying anti-rheumatic drugs available today predominantly act against the inflammatory response of immune cells,\u201d says Masaru Ishii, professor at Osaka University Graduate School of Medicine and corresponding author of the study. \u201cTherapies targeting osteoclasts are limited, largely because we don\u2019t know enough about the osteoclasts involved in RA. We were interested in understanding whether these cells are somehow different from the osteoclasts involved in normal physiological processes.\u201d<\/p>\n<p>Osteoclasts are elusive, residing along the surface of bone under layers of cartilage and tissue. This makes them difficult to isolate in the lab, even with tractable models like mice. To collect the cells, the research group had to develop a surgical technique that allowed them to extract osteoclasts from the femurs of arthritic mice. With osteoclasts securely in hand, they were then able to gather new insights into RA.<\/p>\n<p>\u201cWe tracked precisely how arthritis-inducing osteoclasts develop from their undifferentiated precursor cells,\u201d explains Tetsuo Hasegawa, lead author of the study. \u201cWhile normal osteoclasts are derived from stem cells in the bone marrow, we found that osteoclasts involved in RA come from blood-borne precursors. The circulating precursors enter the joint and differentiate into a unique sub-type of osteoclasts, which are larger and have distinct markers that aren\u2019t seen in other osteoclasts.\u201d<\/p>\n<p>The newly discovered cells, dubbed \u201cAtoMs\u201d (<strong><u>A<\/u><\/strong>r<strong><u>t<\/u><\/strong>hritis-associated <strong><u>o<\/u><\/strong>steoclastogenic <strong><u>M<\/u><\/strong>acrophages), have properties that could be exploitable in the search for new treatments. In one example highlighted by the study, the researchers found that AtoMs have high levels of a protein (called FoxM1) known to make cells invade nearby tissue. They speculated that by getting rid of this hallmark protein\u2014splitting the AtoM, if you will\u2014they could perhaps quell its arthritic tendencies. This is indeed what they found: when FoxM1 was chemically or genetically disrupted in AtoMs, arthritic mice showed reduced bone destructions in their joints.<\/p>\n<p>\u201cOur findings suggest that osteoclasts involved in RA have distinct properties that make them amenable to therapeutic targeting,\u201d says co-author Masaru Ishii. \u201cWhile there is still a lot to learn about this class of cells, we believe the discovery could open the door to new avenues of treatment.\u201d<\/p>\n<p>The article, \u201cIdentification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1\u201d was published in <em>Nature Immunology <\/em>at DOI: 10.1038\/s41590-019-0526-7<\/p>\n<p>&nbsp;<\/p>\n<p class=\"figure\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-5418 size-medium\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/f523dc7eb9d216d6d93339cee7e1a627-400x209.png?_t=1574298433\" alt=\"\" width=\"400\" height=\"209\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/f523dc7eb9d216d6d93339cee7e1a627-400x209.png 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/f523dc7eb9d216d6d93339cee7e1a627.png 687w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/><a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/f523dc7eb9d216d6d93339cee7e1a627.png\"> <span class=\"caption\"><strong>Figure 2. Identification of arthritis-associated osteoclast precursor cells<\/strong><br \/><strong>a<\/strong>, Arthritis-associated osteoclast precursor cells (R3) exist only in the joint tissue and <strong>b<\/strong>, have the capacity to form osteoclasts and resorb bone.<br \/><span class=\"click\">Click to enlarge<\/span><\/span><\/a><\/p>\n<p>&nbsp;<\/p>\n<p class=\"figure\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-5419 size-medium\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/07df9963e250f92e3548b42eb8a1a89b-400x237.png?_t=1574298433\" alt=\"\" width=\"400\" height=\"237\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/07df9963e250f92e3548b42eb8a1a89b-400x237.png 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/07df9963e250f92e3548b42eb8a1a89b.png 697w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/><a href=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/07df9963e250f92e3548b42eb8a1a89b.png\"> <span class=\"caption\"><strong>Figure 3. Inhibition of Foxm1 suppresses osteoclast formation of arthritis-associated osteoclast precursor cells<\/strong><br \/><\/span><span class=\"click\">Click to enlarge<\/span><\/a><\/p>\n<p>&nbsp;<\/p>\n<p><strong>Summary: <\/strong>Rheumatoid arthritis is a chronic, disabling disease in which the joints become swollen and painfully inflamed. Current treatments can only reduce symptoms or slow the disease course. Researchers at Osaka University discovered a new type of osteoclast (bone-dissolving cell) involved in the disease, called AtoMs. The cell type has unique properties that can potentially be targeted by new treatments for rheumatoid arthritis.<\/p>\n<p><strong>Primary Keyword:<\/strong> Biology<br \/><strong>Additional Keywords:<\/strong> Cell Biology, Developmental Biology, Genetics, Molecular Biology<\/p>\n<p>Title:\u201cIdentification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1\u201d\u00a0\u00a0\u00a0<br \/>Journal: Nature Immunology<br \/>Authors: Tetsuo Hasegawa, Junichi Kikuta, Takao Sudo, Yoshinobu Matsuura, Takahiro Matsui, Szandor Simmons, Kosuke Ebina, Makoto Hirao, Daisuke Okuzaki, Yuichi Yoshida, Atsushi Hirao, Vladimir V. Kalinichenko, Kunihiro Yamaoka, Tsutomu Takeuchi, and Masaru Ishii<br \/>DOI: 10.1038\/s41590-019-0526-7<br \/>Funded by: Japan Society for the Promotion of Science, Japan Science and Technology Agency<\/p>\n<p>&nbsp;<\/p>\n<p><strong>About Osaka University <br \/><\/strong>Osaka University was founded in 1931 as one of the seven imperial universities of Japan and now has expanded to one of Japan&#8217;s leading comprehensive universities. The University has now embarked on open research revolution from a position as Japan&#8217;s most innovative university and among the most innovative institutions in the world according to Reuters 2015 Top 100 Innovative Universities and the Nature Index Innovation 2017. The university&#8217;s ability to innovate from the stage of fundamental research through the creation of useful technology with economic impact stems from its broad disciplinary spectrum.<\/p>\n<p>Website: <a href=\"https:\/\/resou.osaka-u.ac.jp\/en\/top\">https:\/\/resou.osaka-u.ac.jp\/en\/top<\/a><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-5442 size-medium\" src=\"http:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/IMG_2364-e1574330364339-400x267.jpg?_t=1574330543\" alt=\"\" width=\"400\" height=\"267\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/IMG_2364-e1574330364339-400x267.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/IMG_2364-e1574330364339-768x513.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2019\/11\/IMG_2364-e1574330364339-1024x684.jpg 1024w\" sizes=\"(max-width: 400px) 100vw, 400px\" \/><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese 2019-11-19 Publish\u00a0 Nature Immunology Researchers at Osaka University discover a new type of  [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":5418,"parent":4390,"menu_order":95,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/5408"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=5408"}],"version-history":[{"count":25,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/5408\/revisions"}],"predecessor-version":[{"id":7607,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/5408\/revisions\/7607"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/4390"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/5418"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=5408"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}