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Original Article | Open Access

Neutralization of excessive levels of active TGF-β1 reduces MSC recruitment and differentiation to mitigate peritendinous adhesion

YuSheng Li1,, Xiao Wang1,, Bo Hu1, Qi Sun1, Mei Wan1, Andrew Carr2, Shen Liu1( ), Xu Cao1( )
Department of Orthopedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Windmill Road, Oxford OX3 7LD, UK

These authors contributed equally: YuSheng Li, Xiao Wang

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Abstract

Peritendinous adhesion formation (PAF) can substantially limit the range of motion of digits. However, the origin of myofibroblasts in PAF tissues is still unclear. In this study, we found that the concentration of active TGF-β1 and the numbers of macrophages, mesenchymal stromal cells (MSCs), and myofibroblasts in human and mouse adhesion tissues were increased. Furthermore, knockout of TGF-β1 in macrophages or TGF-β1R2 in MSCs inhibited PAF by reducing MSC and myofibroblast infiltration and collagen Ⅰ and Ⅲ deposition, respectively. Moreover, we found that MSCs differentiated into myofibroblasts to form adhesion tissues. Systemic injection of the TGF-β–neutralizing antibody 1D11 during the granulation formation stage of PAF significantly reduced the infiltration of MSCs and myofibroblasts and, subsequently, PAF. These results suggest that macrophage-derived TGF-β1 recruits MSCs to form myofibroblasts in peritendinous adhesions. An improved understanding of PAF mechanisms could help identify a potential therapeutic strategy.

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Bone Research
Volume 11,
December 2023
Article number: 24
DOI: 10.1038/s41413-023-00252-1
Cite this article:
Li Y, Wang X, Hu B, et al. Neutralization of excessive levels of active TGF-β1 reduces MSC recruitment and differentiation to mitigate peritendinous adhesion. Bone Research, 2023, 11: 24. https://doi.org/10.1038/s41413-023-00252-1

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Received: 22 July 2022
Revised: 31 January 2023
Accepted: 10 February 2023
Published: 08 May 2023
© The Author(s) 2023

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