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The metabolism of meningiomas is little known, so few effective treatment options other than surgery and radiation are available, and the targets for treatment of recurrence are not well defined. The Aim of this paper is to find the therapeutic target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The effects of bone morphogenetic protein (BMP) signal inhibitor (K02288) and upstream regulator Gremlin2 (GREM2) on meningioma\u2019s growth and senescence were examined. In brief, we examined as follows: 1) Proliferation assay by inhibiting BMP signaling. 2) Comprehensive analysis of forced expression GREM2.3) Correlation between GREM2 mRNA expression and proliferation marker in 87 of our clinical samples. 4) Enrichment analysis between GREM2 high\/low expressed groups using RNA-seq data (42 cases) from the public database GREIN. 5) Changes in metabolites and senescence markers associated with BMP signal suppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Inhibitors of BMP receptor (BMPR1A) and forced expression of GREM2 shifted tryptophan metabolism from kynurenine\/quinolinic acid production to serotonin production in malignant meningiomas, reduced NAD\u2009+\u2009\/NADH production, decreased gene cluster expression involved in oxidative phosphorylation, and caused decrease in ATP. Finally, malignant meningiomas underwent cellular senescence, decreased proliferation, and eventually formed psammoma bodies. Reanalyzed RNA-seq data of clinical samples obtained from GREIN showed that increased expression of GREM2 decreased the expression of genes involved in oxidative phosphorylation, similar to our experimental results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The GREM2-BMPR1A-tryptophan metabolic pathway in meningiomas is a potential new therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11060-024-04625-2","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T05:02:26Z","timestamp":1709701346000},"page":"455-465","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of BMP signaling pathway induced senescence and calcification in anaplastic meningioma"],"prefix":"10.1007","volume":"167","author":[{"given":"Kiyotaka","family":"Yokogami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Mizuguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Takeshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"4625_CR1","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1097\/00006123-199904000-00028","volume":"44","author":"DR Pieper","year":"1999","unstructured":"Pieper DR, Al-Mefty O, Hanada Y, Buechner D (1999) Hyperostosis associated with meningioma of the cranial base: secondary changes or tumor invasion. 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This study was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients for the usage of samples.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}