Cyclopamine targeting hedgehog modulates nuclear control of the osteoblast activity

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dc.contributor.authorda Costa Fernandes, Célio J. [UNESP]
dc.contributor.authorFerreira, Marcel Rodrigues [UNESP]
dc.contributor.authorZambuzzi, Willian Fernando [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2023-07-29T13:49:04Z
dc.date.available2023-07-29T13:49:04Z
dc.date.issued2023-06-01
dc.description.abstractIt is known that cellular events underlying the processes of bone maintenance, remodeling, and repair have their basis in the embryonic production of bone. Shh signaling is widely described developing important morphogenetic control in bone by modifying the activity of osteoblast. Furthermore, identifying whether it is associated with the modulation of nuclear control is very important to be the basis for further applications. Experimentally, osteoblasts were exposed with cyclopamine (CICLOP) considering up to 1 day and 7 days, here considered an acute and chronic responses respectively. Firstly, we have validated the osteogenic model in vitro by exposing the osteoblasts to classical differentiating solution up to 7 days to allow the analysis of alkaline phosphatase and mineralization. Conversely, our data shows that differentiating osteoblasts present higher activity of inflammasome-related genes, while Shh signaling members were lower, suggesting a negative feedback between them. Thereafter, to better know about the role of Shh signaling on this manner, functional assays using CICLOP (5 μM) were performed and the data validates the previously hypothesis that Shh represses inflammasome related genes activities. Altogether, our data supports the anti-inflammatory effect of Shh signaling by suppressing Tnfα, Tgfβ and inflammasome related genes during osteoblast differentiation, and this comprehension might support the understanding the molecular and cellular mechanisms related in bone regeneration by reporting molecular-related osteoblast differentiation.en
dc.description.affiliationDepartament of Chemistry and Biochemistry São Paulo State University (UNESP) Institute of Biosciences, Campus Botucatu
dc.description.affiliationUnespDepartament of Chemistry and Biochemistry São Paulo State University (UNESP) Institute of Biosciences, Campus Botucatu
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPESP: 2014/22689-3
dc.description.sponsorshipIdFAPESP: 2016/08888-9
dc.description.sponsorshipIdFAPESP: 2019/21807-6
dc.description.sponsorshipIdCNPq: 314166/2021-1
dc.identifierhttp://dx.doi.org/10.1016/j.cdev.2023.203836
dc.identifier.citationCells and Development, v. 174.
dc.identifier.doi10.1016/j.cdev.2023.203836
dc.identifier.issn2667-2901
dc.identifier.scopus2-s2.0-85151488752
dc.identifier.urihttp://hdl.handle.net/11449/248620
dc.language.isoeng
dc.relation.ispartofCells and Development
dc.sourceScopus
dc.subjectAnti-inflammatory
dc.subjectASC
dc.subjectCyclopamine
dc.subjectInflammasome
dc.subjectInflammation
dc.subjectOsteoblast
dc.subjectSonic Hedgehog
dc.subjectTGFβ
dc.subjectTNFα
dc.titleCyclopamine targeting hedgehog modulates nuclear control of the osteoblast activityen
dc.typeArtigo

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Artigos - Química e Bioquímica - IBB