Dataset Information

Depleting transforming growth factor beta receptor 2 signalling in the cartilage of itga1-null mice attenuates spontaneous knee osteoarthritis.

ABSTRACT:

Objectives

Integrin α1β1 protects against osteoarthritis (OA) when it is upregulated in the superficial zone of cartilage in the early stages of disease. However, the mechanism behind this protection is unknown. Integrin α1β1 moderates transforming growth factor β receptor II (TGFBR2) signalling, a critical regulator of chondrocyte anabolic activity. To this end, mice lacking integrin α1β1 have increased baseline activation of TGFBR2 signalling and overall fibrosis. The purpose of this study was to evaluate the interplay between integrin α1β1 and TGFBR2 in the development of spontaneous OA. We hypothesized that dampening TGFBR2 signalling in the cartilage of itga1-null mice would attenuate OA.

Methods

Behavioural and histological manifestations of spontaneous knee OA were measured at 4, 8, 12 and 16 months in mice with and without a ubiquitous itga1 deletion and with and without a tamoxifen-induced cartilage specific TGFBR2 depletion.

Results

Knee cartilage degeneration, collateral ligament ossification and pain responses increased with age. Itga1-null mice with intact TGFBR2 signalling developed earlier and more severe OA compared to controls. In agreement with our hypothesis, depleting TGFBR2 signalling in the cartilage of itga1-null mice attenuated OA progression.

Conclusion

Intact TGFBR2 signalling drives early and worse knee OA in itga1-null mice. This result supports the hypothesis that the increased expression of integrin α1β1 by superficial zone chondrocytes early in OA development dampens TGFBR2 signalling and thus protects against degeneration.

SUBMITTER: St Amant J

PROVIDER: S-EPMC10462827 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Depleting transforming growth factor beta receptor 2 signalling in the cartilage of <i>itga1</i>-null mice attenuates spontaneous knee osteoarthritis.

St Amant Jennifer J Michaud Jana J Hinds Daniel D Coyle Madison M Pozzi Ambra A Clark Andrea L AL

Osteoarthritis and cartilage open 20230812 4

<h4>Objectives</h4>Integrin α1β1 protects against osteoarthritis (OA) when it is upregulated in the superficial zone of cartilage in the early stages of disease. However, the mechanism behind this protection is unknown. Integrin α1β1 moderates transforming growth factor β receptor II (TGFBR2) signalling, a critical regulator of chondrocyte anabolic activity. To this end, mice lacking integrin α1β1 have increased baseline activation of TGFBR2 signalling and overall fibrosis. The purpose of this s ...[more]

PMID: 37649532

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