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Red Algae Alters Expression of Inflammatory Pathways in an Osteoarthritis In Vitro Co-Culture

Shane Heffernan Orcid Logo, Mark Waldron Orcid Logo, Kirsty Meldrum, Stephen Evans Orcid Logo, Gill Conway Orcid Logo

Pharmaceuticals, Volume: 18, Issue: 3, Start page: 315

Swansea University Authors: Shane Heffernan Orcid Logo, Mark Waldron Orcid Logo, Kirsty Meldrum, Stephen Evans Orcid Logo, Gill Conway Orcid Logo

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DOI (Published version): 10.3390/ph18030315

Abstract

Background/Objectives: Osteoarthritis (OA) is one of the most prevalent chronic conditions and significantly contributes to local and global disease burden. Common pharmaceuticals that are used to treat OA cause significant side effects, thus non-pharmaceutical bioactive alternatives have been devel...

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Published in: Pharmaceuticals
ISSN: 1424-8247
Published: MDPI AG 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa68959
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Common pharmaceuticals that are used to treat OA cause significant side effects, thus non-pharmaceutical bioactive alternatives have been developed that can impact OA symptoms without severe side-effects. One such alternative is the Red Algae Lithothamnion species (Litho). However, there is little mechanistic knowledge of its potential to effect OA gene expression, and a human in vitro model using commercially available cell lines to test its effectiveness has yet to be developed. Methods: Human osteoblast (hFOB 1.19. CRL-11372) and chondrocyte (C28/I2) cell lines were co-cultured indirectly using transwells. IL1-&#x3B2; was used to induce an inflammatory state and gene expression profiles following treatment were the primary outcome. Conclusion: Results indicated that the model was physiologically relevant, remained viable over at least seven days, untreated or following induction of an inflammatory state while maintaining hFOB 1.19. and C28/I2 cell phenotypic characteristics. Following treatment, Litho reduced the expression of inflammatory and pain associated genes, most notably IL-1&#x3B2;, IL-6, PTGS2 (COX-2) and C1qTNF2 (CTRP2). Confirmatory analysis with droplet digital PCR (ddPCR) revealed that Il-1&#x3B2; induced a significant reduction in C1qTNF2 at 7 days which was ameliorated with Litho treatment. These data present a novel and replicable co-culture model of inflammatory OA that can be used to investigate bioactive nutraceuticals. For the first time, this model demonstrated a reduction in C1qTNF2 expression that was mitigated by Red Algae Lithothamnion species.</abstract><type>Journal Article</type><journal>Pharmaceuticals</journal><volume>18</volume><journalNumber>3</journalNumber><paginationStart>315</paginationStart><paginationEnd/><publisher>MDPI AG</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>1424-8247</issnElectronic><keywords>Red Algae; gene expression; inflammation; osteoarthritis; in vitro</keywords><publishedDay>24</publishedDay><publishedMonth>2</publishedMonth><publishedYear>2025</publishedYear><publishedDate>2025-02-24</publishedDate><doi>10.3390/ph18030315</doi><url/><notes/><college>COLLEGE NANME</college><department>Engineering and Applied Sciences School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>EAAS</DepartmentCode><institution>Swansea University</institution><apcterm>Other</apcterm><funders>This research was partly funded by Nordic Medical Ltd., Office A303-4, Tower Bridge Business Complex, 100 Clements Road, London, SE16 4DG (Grant code 106381), the Higher Education Funding Council for Wales RWIF fund (Grant code #EE16) and institutionally via Swansea University, Applied Sports Science Technology and Medicine Research Centre. 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spelling 2025-03-11T16:10:03.2067967 v2 68959 2025-02-24 Red Algae Alters Expression of Inflammatory Pathways in an Osteoarthritis In Vitro Co-Culture 72c0b36891dfbec0378c0d0f7916e807 0000-0002-3297-9335 Shane Heffernan Shane Heffernan true false 70db7c6c54d46f5e70b39e5ae0a056fa 0000-0002-2720-4615 Mark Waldron Mark Waldron true false bbb7bd27bfa3c6ffc73da8facfebc793 Kirsty Meldrum Kirsty Meldrum true false cfca981bdfb8492873a48cc1629def9a 0000-0002-5352-9800 Stephen Evans Stephen Evans true false e33e0ee5a076ad91fe6615117caa1800 0000-0002-5991-0960 Gill Conway Gill Conway true false 2025-02-24 EAAS Background/Objectives: Osteoarthritis (OA) is one of the most prevalent chronic conditions and significantly contributes to local and global disease burden. Common pharmaceuticals that are used to treat OA cause significant side effects, thus non-pharmaceutical bioactive alternatives have been developed that can impact OA symptoms without severe side-effects. One such alternative is the Red Algae Lithothamnion species (Litho). However, there is little mechanistic knowledge of its potential to effect OA gene expression, and a human in vitro model using commercially available cell lines to test its effectiveness has yet to be developed. Methods: Human osteoblast (hFOB 1.19. CRL-11372) and chondrocyte (C28/I2) cell lines were co-cultured indirectly using transwells. IL1-β was used to induce an inflammatory state and gene expression profiles following treatment were the primary outcome. Conclusion: Results indicated that the model was physiologically relevant, remained viable over at least seven days, untreated or following induction of an inflammatory state while maintaining hFOB 1.19. and C28/I2 cell phenotypic characteristics. Following treatment, Litho reduced the expression of inflammatory and pain associated genes, most notably IL-1β, IL-6, PTGS2 (COX-2) and C1qTNF2 (CTRP2). Confirmatory analysis with droplet digital PCR (ddPCR) revealed that Il-1β induced a significant reduction in C1qTNF2 at 7 days which was ameliorated with Litho treatment. These data present a novel and replicable co-culture model of inflammatory OA that can be used to investigate bioactive nutraceuticals. For the first time, this model demonstrated a reduction in C1qTNF2 expression that was mitigated by Red Algae Lithothamnion species. Journal Article Pharmaceuticals 18 3 315 MDPI AG 1424-8247 Red Algae; gene expression; inflammation; osteoarthritis; in vitro 24 2 2025 2025-02-24 10.3390/ph18030315 COLLEGE NANME Engineering and Applied Sciences School COLLEGE CODE EAAS Swansea University Other This research was partly funded by Nordic Medical Ltd., Office A303-4, Tower Bridge Business Complex, 100 Clements Road, London, SE16 4DG (Grant code 106381), the Higher Education Funding Council for Wales RWIF fund (Grant code #EE16) and institutionally via Swansea University, Applied Sports Science Technology and Medicine Research Centre. KM would like to acknowledge salary funding from the UKRI RESPIRE study (Grant No. NE/W002264/1). 2025-03-11T16:10:03.2067967 2025-02-24T16:00:39.0926234 Faculty of Science and Engineering School of Engineering and Applied Sciences - Sport and Exercise Sciences Shane Heffernan 0000-0002-3297-9335 1 Mark Waldron 0000-0002-2720-4615 2 Kirsty Meldrum 3 Stephen Evans 0000-0002-5352-9800 4 Gill Conway 0000-0002-5991-0960 5 68959__33668__f34640e6d2464abc964e1dd1deb94640.pdf 68959.pdf 2025-02-24T16:07:19.3819681 Output 1676789 application/pdf Version of Record true © 2025 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. true eng https://creativecommons.org/license
title Red Algae Alters Expression of Inflammatory Pathways in an Osteoarthritis In Vitro Co-Culture
spellingShingle Red Algae Alters Expression of Inflammatory Pathways in an Osteoarthritis In Vitro Co-Culture
Shane Heffernan
Mark Waldron
Kirsty Meldrum
Stephen Evans
Gill Conway
title_short Red Algae Alters Expression of Inflammatory Pathways in an Osteoarthritis In Vitro Co-Culture
title_full Red Algae Alters Expression of Inflammatory Pathways in an Osteoarthritis In Vitro Co-Culture
title_fullStr Red Algae Alters Expression of Inflammatory Pathways in an Osteoarthritis In Vitro Co-Culture
title_full_unstemmed Red Algae Alters Expression of Inflammatory Pathways in an Osteoarthritis In Vitro Co-Culture
title_sort Red Algae Alters Expression of Inflammatory Pathways in an Osteoarthritis In Vitro Co-Culture
author_id_str_mv 72c0b36891dfbec0378c0d0f7916e807
70db7c6c54d46f5e70b39e5ae0a056fa
bbb7bd27bfa3c6ffc73da8facfebc793
cfca981bdfb8492873a48cc1629def9a
e33e0ee5a076ad91fe6615117caa1800
author_id_fullname_str_mv 72c0b36891dfbec0378c0d0f7916e807_***_Shane Heffernan
70db7c6c54d46f5e70b39e5ae0a056fa_***_Mark Waldron
bbb7bd27bfa3c6ffc73da8facfebc793_***_Kirsty Meldrum
cfca981bdfb8492873a48cc1629def9a_***_Stephen Evans
e33e0ee5a076ad91fe6615117caa1800_***_Gill Conway
author Shane Heffernan
Mark Waldron
Kirsty Meldrum
Stephen Evans
Gill Conway
author2 Shane Heffernan
Mark Waldron
Kirsty Meldrum
Stephen Evans
Gill Conway
format Journal article
container_title Pharmaceuticals
container_volume 18
container_issue 3
container_start_page 315
publishDate 2025
institution Swansea University
issn 1424-8247
doi_str_mv 10.3390/ph18030315
publisher MDPI AG
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Sport and Exercise Sciences{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Sport and Exercise Sciences
document_store_str 1
active_str 0
description Background/Objectives: Osteoarthritis (OA) is one of the most prevalent chronic conditions and significantly contributes to local and global disease burden. Common pharmaceuticals that are used to treat OA cause significant side effects, thus non-pharmaceutical bioactive alternatives have been developed that can impact OA symptoms without severe side-effects. One such alternative is the Red Algae Lithothamnion species (Litho). However, there is little mechanistic knowledge of its potential to effect OA gene expression, and a human in vitro model using commercially available cell lines to test its effectiveness has yet to be developed. Methods: Human osteoblast (hFOB 1.19. CRL-11372) and chondrocyte (C28/I2) cell lines were co-cultured indirectly using transwells. IL1-β was used to induce an inflammatory state and gene expression profiles following treatment were the primary outcome. Conclusion: Results indicated that the model was physiologically relevant, remained viable over at least seven days, untreated or following induction of an inflammatory state while maintaining hFOB 1.19. and C28/I2 cell phenotypic characteristics. Following treatment, Litho reduced the expression of inflammatory and pain associated genes, most notably IL-1β, IL-6, PTGS2 (COX-2) and C1qTNF2 (CTRP2). Confirmatory analysis with droplet digital PCR (ddPCR) revealed that Il-1β induced a significant reduction in C1qTNF2 at 7 days which was ameliorated with Litho treatment. These data present a novel and replicable co-culture model of inflammatory OA that can be used to investigate bioactive nutraceuticals. For the first time, this model demonstrated a reduction in C1qTNF2 expression that was mitigated by Red Algae Lithothamnion species.
published_date 2025-02-24T08:13:49Z
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