{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:45:09Z","timestamp":1791380709522,"version":"4.3.3"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103028"],"award-info":[{"award-number":["82103028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>A bone\u2010invasive pituitary adenoma exhibits aggressive behavior, leading to a worse prognosis. We have found that TNF\u2010\u03b1 promotes bone invasion by facilitating the differentiation of osteoclasts, however, before bone\u2010invasive pituitary adenoma invades bone tissue, it needs to penetrate the dura mater, and this mechanism is not yet clear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed transcriptome microarrays on specimens of bone\u2010invasive pituitary adenomas (BIPAs) and noninvasive pituitary adenomas (NIPAs) and conducted differential expressed gene analysis and enrichment analysis. We altered the expression of TNF\u2010\u03b1 through plasmids, then validated the effects of TNF\u2010\u03b1 on GH3 cells and verified the efficacy of the TNF\u2010\u03b1 inhibitor SPD304. Finally, the effects of TNF\u2010\u03b1 were validated in in\u00a0vivo experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pathway act work showed that the MAPK pathway was significantly implicated in the pathway network. The expression of TNF\u2010\u03b1, MMP9, and p\u2010p38 is higher in BIPAs than in NIPAs. Overexpression of TNF\u2010\u03b1 elevated the expression of MAPK pathway proteins and MMP9 in GH3 cells, as well as promoted proliferation, migration, and invasion of GH3 cells. Flow cytometry indicated that TNF\u2010\u03b1 overexpression increased the G2 phase ratio in GH3 cells and inhibited apoptosis. The expression of MMP9 was reduced after blocking the P38 MAPK pathway; overexpression of MMP9 promoted invasion of GH3 cells. In\u00a0vivo experiments confirm that the TNF\u2010\u03b1 overexpression group has larger tumor volumes. SPD304 was able to suppress the effects caused by TNF\u2010\u03b1 overexpression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Bone\u2010invasive pituitary adenoma secretes higher levels of TNF\u2010\u03b1, which then acts on itself in an autocrine manner, activating the MAPK pathway and promoting the expression of MMP9, thereby accelerating the membrane invasion process. SPD304 significantly inhibits the effect of TNF\u2010\u03b1 and may be applied in the clinical treatment of bone\u2010invasive pituitary adenoma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14749","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T13:53:44Z","timestamp":1715608424000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["TNF\u2010\u03b1 can promote membrane invasion by activating the MAPK\/MMP9 signaling pathway through autocrine in bone\u2010invasive pituitary adenoma"],"prefix":"10.1111","volume":"30","author":[{"given":"Xinzhi","family":"Wu","sequence":"first","affiliation":[{"name":"Beijing Neurosurgical Institute Capital Medical University  Beijing China"},{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing 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