The absence of oestrogen receptor beta disturbs collagen I type deposition during Achilles tendon healing by regulating the IRF5-CCL3 axis

Xuting Bian; Tianyao Liu; Mingyu Yang; Chengyi Gu; Gang He; Mei Zhou; Hong Tang; Kang Lu; Fan Lai; Feng Wang; Qiandong Yang; Jan Åke Gustafsson; Xiaotang Fan; Kanglai Tang

doi:10.1111/jcmm.15592

The absence of oestrogen receptor beta disturbs collagen I type deposition during Achilles tendon healing by regulating the IRF5-CCL3 axis

Xuting Bian, Tianyao Liu, Mingyu Yang, Chengyi Gu, Gang He, Mei Zhou, Hong Tang, Kang Lu, Fan Lai, Feng Wang, Qiandong Yang, Jan Åke Gustafsson, Xiaotang Fan, Kanglai Tang

Houston Methodist

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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)
Pages (from-to)	9925-9935
Number of pages	11
Journal	Journal of Cellular and Molecular Medicine
Volume	24
Issue number	17
DOIs	https://doi.org/10.1111/jcmm.15592
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

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10.1111/jcmm.15592

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Bian, X., Liu, T., Yang, M., Gu, C., He, G., Zhou, M., Tang, H., Lu, K., Lai, F., Wang, F., Yang, Q., Gustafsson, J. Å., Fan, X., & Tang, K. (2020). The absence of oestrogen receptor beta disturbs collagen I type deposition during Achilles tendon healing by regulating the IRF5-CCL3 axis. Journal of Cellular and Molecular Medicine, 24(17), 9925-9935. https://doi.org/10.1111/jcmm.15592

Bian, X, Liu, T, Yang, M, Gu, C, He, G, Zhou, M, Tang, H, Lu, K, Lai, F, Wang, F, Yang, Q, Gustafsson, JÅ, Fan, X & Tang, K 2020, 'The absence of oestrogen receptor beta disturbs collagen I type deposition during Achilles tendon healing by regulating the IRF5-CCL3 axis', Journal of Cellular and Molecular Medicine, vol. 24, no. 17, pp. 9925-9935. https://doi.org/10.1111/jcmm.15592

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title = "The absence of oestrogen receptor beta disturbs collagen I type deposition during Achilles tendon healing by regulating the IRF5-CCL3 axis",

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.",

keywords = "Achilles tendon healing, IRF5-CCL3 axis, collagen type I, oestrogen receptor β",

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AU - Gu, Chengyi

AU - He, Gang

AU - Zhou, Mei

AU - Tang, Hong

AU - Lu, Kang

AU - Lai, Fan

AU - Wang, Feng

AU - Yang, Qiandong

AU - Gustafsson, Jan Åke

AU - Fan, Xiaotang

AU - Tang, Kanglai

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The absence of oestrogen receptor beta disturbs collagen I type deposition during Achilles tendon healing by regulating the IRF5-CCL3 axis

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Keywords

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