Fig 1: Decreased Sema3A secretion with sensory nerve dysfunction in aging and muscle atrophic mice. (A) ELISA of serum Sema3A levels in mice at different ages, i.e., 7, 35, and 68 weeks old. (B) ELISA of serum Sema3A levels after BTxA-induced muscle dysfunction. (C) Chemogenetic activation of BLACaMKII neurons after muscle paralysis. (D) ELISA of serum Sema3A levels in BTxA model after chemogenetic activation of BLACaMKII neurons. (E) Representative immunofluorescent staining images of CGRP (green) in femurs of saline- or BTxA-treated mice. Scale bar, 50 μm. (F) Representative immunofluorescent staining images of CGRP (green) in tibia after chemogenetic manipulation of BLACaMKII neurons. Scale bar, 50 μm. (G) Quantitative analysis of CGRP+-nerve fibers in BTxA-injected mouse models. (H) Quantitative analysis of CGRP+-nerve fibers in hM3Dq vs. mCherry group of BTxA-injected mice. All data represent mean ± SD. Statistical analysis was assessed using student t-tests for panel (D) and one-way ANOVA followed Tukey comparison test for panels (A,B). *P < 0.05, **P < 0.01, ****P < 0.0001.
Fig 2: Clinical cases for potential application of Sema3A as a prognostic signal of bone loss. (A) Correlation between BMD (T-score) and age (years) in 18 patients. (B) Correlation between BMD (T-score) and Sema3A level in 18 patients. (C) Serum Sema3A level between normal BMD group (T-score > –1) and low BMD group (T-score ≤ –1). (D) Correlation between BMD (T-score) and Sema3A level in 18 patients. (E) Correlation between BMD (T-score) and Sema3A level in male group. (F) Correlation between BMD (T-score) and Sema3A level in female group. For all clinical data, linear regression models were used to explore the correlation between two variables. P < 0.05 was considered significant. (G) Basolateral amygdala (BLA) mediates mechanosensory role of bone in response to mechanical unloading.
Fig 3: SEMA3A increases in patients with DOR. SEMA3A levels in HLT and patients with DOR. Significance was calculated using unpaired t-test and expressed as a p value < 0.05. Data below the sensitivity of the kit were excluded.
Fig 4: SEMA3A increases in patients with DOR who responded better to ovarian stimulation. (A) SEMA3A levels in patients with DOR who were responsive or unresponsive to fertilization procedures. βneg: negative-βhCG; βpos: positive-βhCG; CC: cancelled cycle. Significance was calculated using ordinary one-way ANOVA followed by Tukey’s multiple comparisons test and expressed as p value < 0.05. Data below the sensitivity of the ELISA kit were excluded from the analysis. Spearman’s correlation analysis between SEMA3A and E2 (B), the number of follicles before trigger (C), and mature oocytes (MII oocytes) (D) after hormonal stimulation in women with DOR. R = Spearman’s correlation coefficient; the confidence interval (CI) was set at 95%; p values are reported in the graph. * p < 0.05; ** p < 0.01; *** p < 0.001.
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