Abraham, David;
(2025)
Sex specific knee joint soft tissue mineralization
with fibrillin-1 mutation in male tight skin mice.
European Cells & Materials
10.22203/eCM.v052a03.
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Abstract
Background: Articular 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.
| Type: | Article |
|---|---|
| Title: | Sex specific knee joint soft tissue mineralization with fibrillin-1 mutation in male tight skin mice |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.22203/eCM.v052a03 |
| Language: | English |
| Additional information: | Copyright policy: © 2025 The Author(s). Published by Forum Multimedia Publishing, LLC. This article is distributed in accordance with Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Ossification, articular pathology, mouse mutant, fibrillin-1, osteoarthritis, mechanical loading. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10211667 |
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