{"id":9600,"date":"2026-02-27T09:00:37","date_gmt":"2026-02-27T00:00:37","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/eng\/?page_id=9600"},"modified":"2026-02-27T09:41:14","modified_gmt":"2026-02-27T00:41:14","slug":"tsumaki2026-2-26","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2025year\/tsumaki2026-2-26","title":{"rendered":"Nanao Horike, Takahiro Nemoto, Masahito Ikawa, Noriyuki Tsumaki\u226aTissue Biochemistry\u226b <span>Excess FGFR3 signaling in achondroplasia disrupts turnover of resting zone chondrocytes via CREB signaling<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li><a href=\"https:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2025year\/tsumaki2026-2-26\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><span class=\"lineFrame\">Nature Communications<\/span><\/p>\n<p><em>Researchers from The University of Osaka have identified the importance of the signaling molecule and pathways for healthy bone growth, highlighting potential novel treatments for achondroplasia<\/em><em>.<\/em><\/p>\n<p class=\"figure\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-9560 size-full\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/02\/tsumaki202512_ENfig1.png?_t=1770087430\" alt=\"\" width=\"367\" height=\"321\" \/><br \/>Figure 1. Caption: Histology of growth plate cartilage of achondroplasia model mice in which FGFR3 is overactivated. This study identified SPONDIN1 as a marker for CREB activity. Resting zone was expanded and expressed high level of SPONDIN1 in the model mice.<br \/>Credit: 2025, Nanao Horike et al., Excess FGFR3 signaling in achondroplasia disrupts turnover of resting zone chondrocytes via CREB signaling, Nature Communications<\/p>\n<div class=\"TextBlock\">\n<p>Achondroplasia, also known as short-limb dwarfism, is associated with neurological symptoms and complications due to narrowing of the skeletal structures surrounding the spinal cord. Despite achondroplasia being the most common cause of dwarfism, the mechanisms underlying the condition are unclear, meaning that current treatment options are insufficient.<br \/>Now, a team at The University of Osaka has created a mouse model of achondroplasia that has advanced understanding of both healthy and abnormal bone growth, highlighting potential therapeutic targets. The findings of their research are due to be published in Nature Communications.<br \/>By tracking cell proliferation, the team identified a signaling molecule called FGFR3 and a pathway called CREB as key in regulating bone growth. Growing bones possess a \u2018growth plate\u2019 that consists of three distinct layers of chondrocytes, or cartilage cells, known as the resting, proliferating, and hypertrophic zones. Cells move between these zones, dividing into the proliferating zone and then increasing in size in the hypertrophic zone, resulting in healthy bone growth.<br \/>The mouse model revealed that cells carrying the genetic mutation associated with achondroplasia accumulate in the resting zone and show abnormal behaviors, which included abnormal patterns of division, migration into the proliferating zone, and gene expression.<br \/>\u201cA major challenge in studying the process of chondrocyte differentiation is the difficulty in identifying and analyzing cells at each stage,\u201d explains lead author, Nanao Horike. \u201cHere, we overcame this problem using single-cell RNA sequencing. This allows the genes active in a single cell to be identified, and thus each stage of differentiation to be characterized.\u201d<br \/>This analysis compared chondrocytes with and without the genetic mutation causing achondroplasia and showed that the major differences were in how cells behaved in the resting zone. This is particularly significant, as previous studies and treatments for this condition have focused exclusively on cells in the proliferating and hypertrophic zones.<br \/>\u201cThe increased FGFR3 expression observed in achondroplastic chondrocytes affects signaling through the CREB pathway,\u201d notes senior author, Noriyuki Tsumaki. \u201cInhibition of this pathway using a drug called CREB inhibitor 666-15 restored the typical signaling behavior of cells in the growth plate and increased the length of the bone. This tells us that drugs targeting this pathway could have a significant therapeutic effect in achondroplasia.\u201d<br \/>This study therefore represents a significant advance in our understanding of how chondrocytes differentiate as bones grow. Moreover, additional discoveries about FGFR3 expression and the CREB pathway provides novel therapeutic targets that, with future research, could prove significant in drug development to minimize the debilitating conditions associated with achondroplasia.<\/p>\n<\/div>\n<p>###<\/p>\n<p>The article, \u201cExcess FGFR3 signaling in achondroplasia disrupts turnover of resting zone chondrocytes via CREB signaling,\u201d was published in Nature Communications at DOI:<a href=\"https:\/\/doi.org\/10.1038\/s41467-026-69507-9\">https:\/\/doi.org\/10.1038\/s41467-026-69507-9<\/a><\/p>\n<p><strong>Summary:<\/strong> Researchers from The University of Osaka have developed a mouse model for achondroplasia. The model identified the importance of a signaling molecule called FGFR3 and a pathway called CREB in regulating bone growth. This pathway is also at least partially responsible for the pathology associated with achondroplasia and the associated debilitating conditions and neurological symptoms. Their findings advance our understanding of the process of bone growth and provide novel therapeutic targets for achondroplasia.<\/p>\n<p><strong>Tweet<\/strong>: CREB: The pathway for growth? Researchers at @UOsaka reveal advanced insights into healthy bone growth through a mouse model of achondroplasia<br \/>@UOsaka_en<\/p>\n<p><strong>Primary Keyword<\/strong>: Health and medicine<\/p>\n<p><strong>Additional Keyword<\/strong>: Bone formation, bones, downstream signaling, FGF pathway, genetic disorders, growth factor pathways, signaling pathways, skeleton<\/p>\n<p><strong>Method of Research<\/strong>: Experimental study<\/p>\n<p><strong>Subject of Research<\/strong>: Cells<\/p>\n<p><strong>Title<\/strong>: \u201cExcess FGFR3 signaling in achondroplasia disrupts turnover of resting zone chondrocytes via CREB signaling\u201d<\/p>\n<p><strong>Journal<\/strong>: <em>Nature Communications<\/p>\n<p><\/em><strong>Authors<\/strong>: Nanao Horike, Seiya Oura, Saeko Koyamatsu, Noriko Tanaka, Yuki Iimori, Kaori Fujita, Takahiro Nemoto, Masahito Ikawa, and Noriyuki Tsumaki<\/p>\n<p><strong>DOI<\/strong>: <a href=\"https:\/\/doi.org\/10.1038\/s41467-026-69507-9\">https:\/\/doi.org\/10.1038\/s41467-026-69507-9<\/a><\/p>\n<p><strong>Funded by<\/strong>: Japan Society for the Promotion of Science<br \/>Ministry of Education, Culture, Sports, Science and Technology<br \/>Japan Agency for Medical Research and Development<\/p>\n<p><strong>Article publication date<\/strong>: 26-FEB-2026\u3000<\/p>\n<p><strong>Related links<\/strong>:<br \/>Noriyuki Tsumaki<br \/><a href=\"https:\/\/researchmap.jp\/cart?lang=en\">https:\/\/researchmap.jp\/cart?lang=en<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Nature Communications Researchers from The University of Osaka have identified the importance [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":9560,"parent":8696,"menu_order":13,"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\/9600"}],"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=9600"}],"version-history":[{"count":1,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/9600\/revisions"}],"predecessor-version":[{"id":9601,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/9600\/revisions\/9601"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/8696"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/9560"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=9600"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}