{"id":25465,"date":"2020-01-21T12:31:43","date_gmt":"2020-01-21T20:31:43","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=25465"},"modified":"2020-02-27T08:53:38","modified_gmt":"2020-02-27T16:53:38","slug":"drug-combo-reverses-arthritis-in-rats","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/drug-combo-reverses-arthritis-in-rats\/","title":{"rendered":"Drug combo reverses arthritis in rats"},"content":{"rendered":"

LA JOLLA\u2014People with osteoarthritis, or \u201cwear and tear\u201d arthritis, have limited treatment options: pain relievers or joint replacement surgery. Now, Salk researchers have discovered that a powerful combination of two experimental drugs reverses the cellular and molecular signs of osteoarthritis in rats as well as in isolated human cartilage cells. Their results were published in the journal Protein & Cell<\/em><\/a> on January 16, 2020.<\/p>\n

\"The
The top image shows a knee joint in a healthy rat. (Red [surrounding white] indicates cartilage.) The second image from top shows a joint with grade 2 untreated osteoarthritis. The third image shows a joint with osteoarthritis that has worsened from grade 2 to grade 4 after six weeks of placebo therapy. The bottom image shows a joint with osteoarthritis that improved from grade 2 to grade 1 (mild) after six weeks of combination therapy with alphaKlotho and sTGFbR2.<\/p>\n

Click here<\/a> for a high-resolution image.<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

“What\u2019s really exciting is that this is potentially a therapy that can be translated to the clinic quite easily,\u201d says Juan Carlos Izpisua Belmonte<\/a>,<\/u> lead author and a professor in Salk\u2019s Gene Expression Laboratory. \u201cWe are excited to continue refining this promising combination therapy for human use.”<\/p>\n

Affecting 30 million adults, osteoarthritis is the most common joint disorder in the United States and its prevalence is expected to rise in coming years due to the aging population and increasing rate of obesity. The disease is caused by gradual changes to cartilage that cushions bones and joints. During aging and repetitive stress, molecules and genes in the cells of this articular cartilage change, eventually leading to the breakdown of the cartilage and the overgrowth of underlying bone, causing chronic pain and stiffness.<\/p>\n

Previous research had pinpointed two molecules, alpha-KLOTHO and TGF beta receptor 2 (TGF\u03b2R2), as potential drugs to treat osteoarthritis. \u03b1KLOTHO acts on the mesh of molecules surrounding articular cartilage cells, keeping this extra-cellular matrix from degrading. TGF\u03b2R2 acts more directly on cartilage cells, stimulating their proliferation and preventing their breakdown.<\/p>\n

While each drug alone had only moderately curbed osteoarthritis in animal models of the disease, Izpisua Belmonte and his colleagues wondered if the two drugs would act more effectively in concert.<\/p>\n

\u201cWe thought that by mixing these two molecules that work in different ways, maybe we could make something better,\u201d says Paloma Martinez-Redondo, a Salk postdoctoral fellow and co-first author of the new study.<\/p>\n

The researchers treated young, otherwise healthy rats with osteoarthritis with viral particles containing the DNA instructions for making \u03b1KLOTHO and TGF\u03b2R2.<\/p>\n

Six weeks after the treatment, rats that had received control particles had more severe osteoarthritis in their knees, with the disease progressing from stage 2 to stage 4. However, rats that had received particles containing \u03b1KLOTHO and TGF\u03b2R2 DNA showed recovery of their cartilage: the cartilage was thicker, fewer cells were dying, and actively proliferating cells were present. These animals\u2019 disease improved from stage 2 to stage 1, a mild form of osteoarthritis, and no negative side effects were observed.<\/p>\n

\"From
From left: Juan Carlos Izpisua Belmonte, Paloma Martinez-Redondo, Isabel Guillen-Guillen and Pradeep Reddy.<\/p>\n

Click here<\/a> for a high-resolution image.<\/p>\n

Credit: Salk Institute<\/figcaption><\/figure>\n

\u201cFrom the very first time we tested this drug combination on just a few animals, we saw a huge improvement,\u201d says Isabel Guillen-Guillen, also a Salk postdoctoral fellow and the paper\u2019s co-first author. \u201cWe kept checking more animals and seeing the same encouraging results.\u201d<\/p>\n

Further experiments revealed 136 genes that were more active and 18 genes that were less active in the cartilage cells of treated rats compared to control rats. Among those were genes involved in inflammation and immune responses, suggesting some pathways by which the combination treatment works.<\/p>\n

To test the applicability of the drug combination to humans, the team treated isolated human articular cartilage cells with \u03b1KLOTHO and TGF\u03b2R2. Levels of molecules involved in cell proliferation, extra-cellular matrix formation and cartilage cell identity all increased.<\/p>\n

\u201cThat\u2019s not the same as showing how these drugs affect the knee joint in humans, but we think it\u2019s a good sign that this could potentially work for patients,\u201d says Martinez-Redondo.<\/p>\n

The research team plans to develop the treatment further, including investigating whether soluble molecules of the \u03b1KLOTHO and TGF\u03b2R2 proteins can be taken directly, rather than administered through viral particles. They also will study whether the combination of drugs can prevent the development of osteoarthritis before symptoms develop.<\/p>\n

\u201cWe think that this could be a viable treatment for osteoarthritis in humans,\u201d says Pedro Guillen, director of the Clinica CEMTRO and co-corresponding author.<\/p>\n

Other authors were Chao Wang, Javier Prieto, Masakazu Kurita, Fumiyuki Hatanaka, Cuiqing Zhong, Reyna Hernandez-Benitez, Tomoaki Hishida, Takashi Lezaki, Akihisa Sakamoto, Amy Nemeth, Yuriko Hishida, Concepcion Rodriguez Esteban, Kensaku Shojima, Pradeep Reddy, Ling Huang and Maxim Shokhirev of Salk; Noah Davidson and George Church of Harvard University; Estrella Nu\u00f1ez-Delicado of Universidad Cat\u00f3lica San Antonio de Murcia; Josep Campistol of Hospital Clinic of Barcelona; Isabel Guillen-Vicente, Elena Rodriguez-I\u00f1igo, Juan Manuel Lopez-Alcorocho, Marta Guillen-Vicente and Pedro Guillen-Garcia of Clinica CEMTRO; and Guang-Hui Liu of Chinese Academy of Sciences.<\/p>\n","protected":false},"featured_media":0,"template":"","faculty":[85],"disease-research":[146],"class_list":["post-25465","disclosure","type-disclosure","status-publish","hentry","faculty-juan-carlos-izpisua-belmonte","disease-research-aging-and-regenerative-medicine"],"acf":[],"yoast_head":"\nDrug combo reverses arthritis in rats - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/drug-combo-reverses-arthritis-in-rats\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Drug combo reverses arthritis in rats - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014People with osteoarthritis, or \u201cwear and tear\u201d arthritis, have limited treatment options: pain relievers or joint replacement surgery. Now, Salk researchers have discovered that a powerful combination of two experimental drugs reverses the cellular and molecular signs of osteoarthritis in rats as well as in isolated human cartilage cells. Their results were published in the journal Protein & Cell on January 16, 2020.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/es\/news-release\/drug-combo-reverses-arthritis-in-rats\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"article:modified_time\" content=\"2020-02-27T16:53:38+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.salk.edu\/wp-content\/uploads\/2020\/01\/Knee-joint1-1500-300x428.jpg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/drug-combo-reverses-arthritis-in-rats\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/drug-combo-reverses-arthritis-in-rats\\\/\",\"name\":\"Drug combo reverses arthritis in rats - Salk Institute for Biological Studies\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/drug-combo-reverses-arthritis-in-rats\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/drug-combo-reverses-arthritis-in-rats\\\/#primaryimage\"},\"thumbnailUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2020\\\/01\\\/Knee-joint1-1500-300x428.jpg\",\"datePublished\":\"2020-01-21T20:31:43+00:00\",\"dateModified\":\"2020-02-27T16:53:38+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/drug-combo-reverses-arthritis-in-rats\\\/#breadcrumb\"},\"inLanguage\":\"es-MX\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/drug-combo-reverses-arthritis-in-rats\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"es-MX\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/drug-combo-reverses-arthritis-in-rats\\\/#primaryimage\",\"url\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2020\\\/01\\\/Knee-joint1-1500-300x428.jpg\",\"contentUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2020\\\/01\\\/Knee-joint1-1500-300x428.jpg\"},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/drug-combo-reverses-arthritis-in-rats\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.salk.edu\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Drug combo reverses arthritis in rats\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"name\":\"Salk Institute for Biological Studies\",\"description\":\"The Power of Science\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.salk.edu\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"es-MX\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\",\"name\":\"Salk Institute for Biological Studies\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"es-MX\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"contentUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"width\":696,\"height\":696,\"caption\":\"Salk Institute for Biological Studies\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Drug combo reverses arthritis in rats - Salk Institute for Biological Studies","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.salk.edu\/es\/news-release\/drug-combo-reverses-arthritis-in-rats\/","og_locale":"es_MX","og_type":"article","og_title":"Drug combo reverses arthritis in rats - Salk Institute for Biological Studies","og_description":"LA JOLLA\u2014People with osteoarthritis, or \u201cwear and tear\u201d arthritis, have limited treatment options: pain relievers or joint replacement surgery. Now, Salk researchers have discovered that a powerful combination of two experimental drugs reverses the cellular and molecular signs of osteoarthritis in rats as well as in isolated human cartilage cells. Their results were published in the journal Protein & Cell on January 16, 2020.","og_url":"https:\/\/www.salk.edu\/es\/news-release\/drug-combo-reverses-arthritis-in-rats\/","og_site_name":"Salk Institute for Biological Studies","article_modified_time":"2020-02-27T16:53:38+00:00","og_image":[{"url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2020\/01\/Knee-joint1-1500-300x428.jpg","type":"","width":"","height":""}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"4 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.salk.edu\/news-release\/drug-combo-reverses-arthritis-in-rats\/","url":"https:\/\/www.salk.edu\/news-release\/drug-combo-reverses-arthritis-in-rats\/","name":"Drug combo reverses arthritis in rats - Salk Institute for Biological Studies","isPartOf":{"@id":"https:\/\/www.salk.edu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.salk.edu\/news-release\/drug-combo-reverses-arthritis-in-rats\/#primaryimage"},"image":{"@id":"https:\/\/www.salk.edu\/news-release\/drug-combo-reverses-arthritis-in-rats\/#primaryimage"},"thumbnailUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2020\/01\/Knee-joint1-1500-300x428.jpg","datePublished":"2020-01-21T20:31:43+00:00","dateModified":"2020-02-27T16:53:38+00:00","breadcrumb":{"@id":"https:\/\/www.salk.edu\/news-release\/drug-combo-reverses-arthritis-in-rats\/#breadcrumb"},"inLanguage":"es-MX","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.salk.edu\/news-release\/drug-combo-reverses-arthritis-in-rats\/"]}]},{"@type":"ImageObject","inLanguage":"es-MX","@id":"https:\/\/www.salk.edu\/news-release\/drug-combo-reverses-arthritis-in-rats\/#primaryimage","url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2020\/01\/Knee-joint1-1500-300x428.jpg","contentUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2020\/01\/Knee-joint1-1500-300x428.jpg"},{"@type":"BreadcrumbList","@id":"https:\/\/www.salk.edu\/news-release\/drug-combo-reverses-arthritis-in-rats\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.salk.edu\/"},{"@type":"ListItem","position":2,"name":"Drug combo reverses arthritis in rats"}]},{"@type":"WebSite","@id":"https:\/\/www.salk.edu\/#website","url":"https:\/\/www.salk.edu\/","name":"Instituto Salk de Estudios Biol\u00f3gicos","description":"The Power of Science","publisher":{"@id":"https:\/\/www.salk.edu\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.salk.edu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"es-MX"},{"@type":"Organization","@id":"https:\/\/www.salk.edu\/#organization","name":"Instituto Salk de Estudios Biol\u00f3gicos","url":"https:\/\/www.salk.edu\/","logo":{"@type":"ImageObject","inLanguage":"es-MX","@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/","url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","contentUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","width":696,"height":696,"caption":"Salk Institute for Biological Studies"},"image":{"@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/"}}]}},"ACF":{"paper_url":"https:\/\/link.springer.com\/article\/10.1007\/s13238-019-00685-7","journal_title":"Protein & Cell","paper_author_list":"Paloma Martinez-Redondo, Isabel Guillen-Guillen, Noah Davidsohn, Chao Wang, Javier Prieto, Masakazu Kurita, Fumiyuki Hatanaka, Cuiqing Zhong, Reyna Hernandez-Benitez, Tomoaki Hishida, Takashi Lezaki, Akihisa Sakamoto, Amy N. Nemeth, Yuriko Hishida, Concepcion Rodriguez Esteban, Kensaku Shojima, Ling Huang, Maxim Shokhirev, Estrella Nu\u00f1ez-Delicado, Josep M. Campistol, Isabel Guillen-Vicente, Elena Rodriguez-I\u00f1igo, Juan Manuel Lopez-Alcorocho, Marta Guillen-Vicente, George Church, Pradeep Reddy, Pedro Guillen-Garcia, Guang-Hui Liu, Juan Carlos Izpisua Belmonte","doi":"","paper_title":"\u03b1KLOTHO and sTGF\u03b2R2 treatment counteract the osteoarthritic phenotype developed in a rat model","subhead":"A combination of two previously studied osteoarthritis drugs works better than either drug alone, Salk researchers discovered","home_photo":"","listing_photo":"","legacy_boilerplate":[],"hide_boilerplate":[],"disable_date":false,"listing_excerpt":"","descriptive_blurb":"","has_journal_cover":false,"og_image_override":false,"gallery":false},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure\/25465","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":13,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure\/25465\/revisions"}],"predecessor-version":[{"id":25826,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disclosure\/25465\/revisions\/25826"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/media?parent=25465"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/faculty?post=25465"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/es\/wp-json\/wp\/v2\/disease-research?post=25465"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}