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. 2022 Sep 12;13:5338. doi: 10.1038/s41467-022-33006-4

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© The Author(s) 2022

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — a micro-CT images of the trabecular part of distal femur of rat treated with S3-15 shows higher bone density than rat not treated (OVX). Histological analysis of trabecular bone parameters including BV/TV, Tb.Th, Tb.N and Tb.Sp demonstrate that S3-15 improve significantly the morphometric characteristics of trabecular bone. b Serum PINP, CTX-I, OCN, and Glu-Ocn osteoporosis related marker levels were decreased in rats treated with S3-15. c micro-CT images of the trabecular part of distal femur of mouse treated with S3-15 shows higher bone density than mouse not treated (OVX). Histological analysis of trabecular bone parameters including BV/TV, Tb.Th, Tb.N, and Tb.Sp demonstrate that S3-15 improve significantly the morphometric characteristics of trabecular bone. Biomechanical testing shows S3-15 treated mice improving ultimate load. d, e S3-15 can improve the imbalance of immune cell ratio caused by osteoporosis. In peripheral blood total CD3⁺, CD8⁺ and CD3⁺CD8⁺ T cells are decreased in osteoporosis mice, (left). In CD3⁺ T cells subset, osteoporosis mice show an increased percentage of CD3⁺CD4⁺ T cells and a decreased percentage of CD3 + CD8 + T cells, that results in the increased the value of CD3⁺CD4⁺/ CD3⁺CD8⁺(right). S3-15 treatment can reverse those abnormal indicators. f S3-15 alleviating spleens swelling in mice with osteoporosis. g Spleens of sham, OVX and S3-15 treated mice are got and applied splenic lymphocyte transformation experiment. Spleen lymphocyte transforming index is lower in osteoporosis mice than sham mice and can improve to normal level after S3-15 treatment for 4 weeks. Rat number of sham and OVX + S3-15 group, n = 9. Rat number of OVX group, n = 10. In mouse study, n = 8 mice per group. Data are expressed as means ± s.d. Statistical difference for ultimate load was determined by one-way ANOVA followed by Uncorrected Fisher’s LSD, and the others were followed by Tukey’s multiple comparisons test. Significant difference p-value is < 0.05. Scalar bar, 500 μm.