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. 2021 Sep 9;11:17978. doi: 10.1038/s41598-021-97445-7

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Study flow chart. The flow chart shows the experimental design and number of mice used per experiment/outcome in this study for determining (a) the effect of metformin for joint contracture, and (b) the effective time of metformin administration for joint capsular fibrosis. Non-striped upward triangles indicate the histological and immunohistochemical analyses. Striped upward triangles indicate gene expression analysis. Non-Im, mice with non-immobilized knees; Im+/Met−, mice with immobilized knees but no metformin; Im+/Met+, mice with immobilized knees who were administered metformin; Im+/Met 0–4 weeks, mice with immobilized knees and metformin administered from 0 to 4 weeks; Im+/Met 0–2 weeks, mice with immobilized knees and metformin administered from 0 to 2 weeks; Im+/Met 2–4 weeks, mice with immobilized knees and metformin administered from 2 to 4 weeks.