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Immunomodulatory inhibition of osteoclastogenesis by a marine microalgal ethanol fraction targeting T-cells, antigen presentation, and macrophage fate

2025-10-10Journal article Open access
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dc.contributor.authorCarletti, Alessio
dc.contributor.authorPes, Katia
dc.contributor.authorTarasco, Marco
dc.contributor.authorRosa, Joana
dc.contributor.authorPoudel, Sunil
dc.contributor.authorPereira, Hugo
dc.contributor.authorLouro, Bruno
dc.contributor.authorCancela, M. Leonor
dc.contributor.authorLaizé, Vincent
dc.contributor.authorGavaia, Paulo
dc.date.accessioned2025-11-06T13:33:45Z
dc.date.available2025-11-06T13:33:45Z
dc.date.issued2025-10-10
dc.description.abstractBackground: Targeting immune pathways to prevent bone loss represents a promising, yet underexplored therapeutic strategy. Methods: An ethanol-soluble fraction derived from the freeze-dried biomass of the marine microalga Skeletonema costatum (SKLT) was tested for its ability to modulate immune responses and inhibit osteoclastogenesis. Its effects were evaluated in a zebrafish model of bone regeneration, a medaka model of RANKLinduced osteoporosis, and in vitro using murine RAW 264.7 macrophages. Transcriptomic profiling of regenerating fin blastemas at 24 hours postamputation was performed to identify the affected molecular pathways. Results: In zebrafish, SKLT treatment suppressed the recruitment of osteoclast precursors and altered mineralization dynamics. Transcriptomic profiling revealed downregulation of genes involved in inflammation, antigen presentation, T-cell activation, and macrophage commitment towards osteoclastogenesis, accompanied by reduced expression of chemokines and cytokines that promote osteoclast precursor recruitment and fusion. In medaka, SKLT significantly reduced vertebral bone loss and enhanced neural arch mineralization in larvae with high RANKL expression. In vitro, SKLT inhibited proliferation and osteoclastic differentiation of murine RAW 264.7 macrophages exposed to RANKL without inducing cytotoxicity. Conclusion: These findings identify S. costatum as a source of bioactive immunomodulatory compounds capable of interfering with key osteoimmune mechanisms. Beyond providing proof of concept for their therapeutic potential in bone erosive disorders, this work opens avenues for isolating and characterizing the active molecules, optimizing their delivery, and evaluating their efficacy in preclinical mammalian models. Such strategies could expand the repertoire of safe, nutraceutical-based or adjuvant therapies for osteoporosis and other inflammation-driven skeletal diseases, complementing and potentially enhancing current antiresorptive and anabolic treatments.eng
dc.description.sponsorship(grant EAPA/151/2016/BLUEHUMAN; ALG-01-0145-FEDER-02212
dc.identifier.doi10.3389/fimmu.2025.1655321
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/10400.1/27879
dc.language.isoeng
dc.peerreviewedyes
dc.publisherFrontiers Media
dc.relationCentre of Marine Sciences
dc.relationCentre for Marine and Environmental Research
dc.relationCentre of Marine Sciences
dc.relation.ispartofFrontiers in Immunology
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectOsteoimmunology
dc.subjectOsteoporosis
dc.subjectT-cells
dc.subjectAntigen presentation
dc.subjectMacrophages
dc.subjectOsteoclast differentiation
dc.subjectMicroalgae
dc.subjectSkeletonema costatum
dc.titleImmunomodulatory inhibition of osteoclastogenesis by a marine microalgal ethanol fraction targeting T-cells, antigen presentation, and macrophage fateeng
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentre of Marine Sciences
oaire.awardTitleCentre for Marine and Environmental Research
oaire.awardTitleCentre of Marine Sciences
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04326%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0101%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04326%2F2019/PT
oaire.citation.titleFrontiers in Immunology
oaire.citation.volume16
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameCarletti
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person.familyNamePoudel
person.familyNamePereira
person.familyNameLouro
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person.familyNameLaizé
person.familyNameGavaia
person.givenNameAlessio
person.givenNameKatia
person.givenNameMarco
person.givenNameJoana
person.givenNameSunil
person.givenNameHugo
person.givenNameBruno
person.givenNameM. Leonor
person.givenNameVincent
person.givenNamePaulo
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project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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