Abstract
Achilles tendon healing (ATH) remains an unanswered question in the field of sports medicine because it does not produce tissue with homology to the previously uninjured tissue. Oestrogen receptor β (ERβ) is involved in the injury and repair processes of tendons. Our previous study confirmed that ERβ plays a role in the early stage of ATH by affecting adipogenesis, but its role in extracellular matrix (ECM) remodelling is unknown. We established a 4-week Achilles tendon repair model to investigate the mechanism through which ERβ affects ATH at the very beginning of ECM remodelling phase. In vitro studies were performed using tendon-derived stem cells (TDSCs) due to their promising role in tendon healing. Behavioural and biomechanical tests revealed that ERβ-deficient mice exhibit weaker mobility and inferior biomechanical properties, and immunofluorescence staining and qRT-PCR showed that these mice exhibited an erroneous ECM composition, as mainly characterized by decreased collagen type I (Col I) deposition. The changes in gene expression profiles between ERβ-knockout and WT mice at 1 week were analysed by RNA sequencing to identify factors affecting Col I deposition. The results highlighted the IRF5-CCL3 axis, and this finding was verified with CCL3-treated TDSCs. These findings revealed that ERβ regulates Col I deposition during ATH via the IRF5-CCL3 axis.
Original language | English (US) |
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Pages (from-to) | 9925-9935 |
Number of pages | 11 |
Journal | Journal of Cellular and Molecular Medicine |
Volume | 24 |
Issue number | 17 |
DOIs | |
State | Published - Sep 1 2020 |
Keywords
- Achilles tendon healing
- IRF5-CCL3 axis
- collagen type I
- oestrogen receptor β
ASJC Scopus subject areas
- Molecular Medicine
- Cell Biology