Sex specific knee joint soft tissue mineralization with fibrillin-1 mutation in male tight skin mice

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dc.authorid0000-0002-8782-8016
dc.authorid0000-0003-4470-7465
dc.authorid0000-0003-4346-8861
dc.authorid0000-0001-9431-3742
dc.authorid0000-0001-8952-6057
dc.authorid0000-0002-9563-9418
dc.authorid0000-0002-9224-5253
dc.contributor.authorKeenan, Craig
dc.contributor.authorWang, Xia
dc.contributor.authorDikmen, Tayfun
dc.contributor.authorWen, Y.
dc.contributor.authorRamos-Mucci, Lorenzo
dc.contributor.authorShorter, Emily
dc.contributor.authorAbraham, David
dc.contributor.authorBou-Gharios, George
dc.contributor.authorPoulet, Blandine
dc.date.accessioned2025-09-26T08:02:57Z
dc.date.available2025-09-26T08:02:57Z
dc.date.issued2025
dc.departmentFakülteler, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Histoloji ve Embriyoloji Ana Bilim Dalı
dc.description.abstractArticular soft tissue mineralization and ossification are clear pathological signs of osteoarthritis (OA) joints. However their molecular and cellular aetiologies remain largely unknown. Transforming growth factor beta (TGF-β) family members are known contributors to both pathological ossification and osteoarthritis development. In this study, we used a fibrillin-1 (Fbn1) mutant mouse, the tight skin (TSK) mouse, to define the detrimental effects of abnormal Fbn1 in TSK mice and known high TGF-β activity in joint pathology such as articular soft tissue mineralization and ossification. Methods: Knee joints of male and female TSK and wild-type (WT) littermates were analysed by micro-computed tomography (micro-CT) imaging and histology for articular soft tissue pathologies, as well as OA severity. Both aged (10, 26, 35 and 52 weeks) and following in vivo non-invasive repetitive joint overloading were used. Results: We find that male TSK mice develop spontaneous soft tissue ossification from 26 weeks of age, followed by increased osteoarthritis at 1 year-old. In addition, knee joint overloading induced ligament and meniscal mineralisation and ossification in both WT and TSK male mice, but were significantly more severe in TSK knees, including ossification of the patella ligament and synovial lining. In contrast, female TSK knees did not develop more severe soft tissue mineralisation compared to littermate WT mice in neither aged nor overloaded knees. Conclusions: We conclude that Fbn1 mutation, and possibly overactive TGF-β activity in TSK mice, induce articular soft tissue ossification and osteoarthritis in a sex-specific manner. Further studies are needed to confirm the specific signalling involved and the relative protection from female mice from such pathologies.
dc.description.sponsorshipThis research was funded by Arthritis Research UK (20859), Versus Arthritis (22451), Chinese Scholarship Council, the Medical Research Council (MR/X021068/1), The MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), and the Institute of Aging and Chronic Disease (University of Liverpool). Bu araştırma, Arthritis Research UK (20859), Versus Arthritis (22451), Çin Burs Konseyi, Tıbbi Araştırma Konseyi (MR/X021068/1), MRC-Arthritis Research UK Entegre Kas-İskelet Sistemi Yaşlanması Araştırma Merkezi (CIMA) ve Yaşlanma ve Kronik Hastalıklar Enstitüsü (Liverpool Üniversitesi) tarafından finanse edilmiştir.
dc.identifier.citationKeenan, C., Wang, X., Dikmen, T., Wen, Y., Ramos-Mucci, L., Shorter, E., Abraham, D., Bou-Gharios, G., & Poulet, B. (2025). Sex specific knee joint soft tissue mineralization with fibrillin-1 mutation in male tight skin mice. European Cells and Materials, 52, pp. 34-43. https://doi.org/10.22203/eCM.v052a03
dc.identifier.doi10.22203/eCM.v052a03
dc.identifier.endpage43
dc.identifier.issn1473-2262
dc.identifier.scopusqualityQ2
dc.identifier.startpage34
dc.identifier.urihttps://doi.org/10.22203/eCM.v052a03
dc.identifier.urihttps://hdl.handle.net/20.500.13055/1119
dc.identifier.volume52
dc.identifier.wosWOS:001569251800003
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorDikmen, Tayfun
dc.institutionauthorid0000-0003-4470-7465
dc.language.isoen
dc.publisherForum Multimedia Publishing
dc.relation.ispartofEuropean Cells and Materials
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectOssification
dc.subjectArticular Pathology
dc.subjectMouse Mutant
dc.subjectFibrillin-1
dc.subjectOsteoarthritis
dc.subjectMechanical Loading
dc.titleSex specific knee joint soft tissue mineralization with fibrillin-1 mutation in male tight skin mice
dc.typeArticle
dspace.entity.typePublication

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