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SUMMARY OBJECTIVE: Thyroid neoplasm incidence has increased worldwide, mostly due to the advancements in medical imaging and screening rates. The aberrant Wnt/β-catenin pathway has been identified as a key mechanism, and it has also been related to the metastatic activity of differentiated thyroid cancer. We aimed to verify the difference in the expression of Wnt3a, a canonical activator of the β-catenin signaling, and CDX-2, a transcription factor upregulated by Wnt/β-catenin pathway, in multinodular goiter and differentiated thyroid cancer and to determine their prognostic value. METHODS: We included 194 thyroid tissue surgical specimen and their clinicopathological data: study group (differentiated thyroid cancer, n=154) and control group (multinodular goiter, n=40). Immunohistochemistry (IHC) was performed on formalin-fixed, paraffin-embedded tissue by the primary antibodies Wnt3a and CDX-2. RESULTS: High Wnt3a expression was significantly associated with differentiated thyroid cancer (p=0.031). CDX-2 was negative in all differentiated thyroid cancer cases (100%) and also in multinodular goiter. Wnt3a expression was significantly associated with tumors ≤20 mm (p=0.044) and with the absence of capsule invasion (p=0.031). The multivariate analyses suggested that older age (≥55), independent of capsular invasion and tumor size, was an independent prognostic factor for Wnt3a expression (p=0.058). CONCLUSIONS: Wnt3a expression but not CDX-2 is correlated with differentiated thyroid cancer samples in comparison to multinodular goiter. Although its prognostic value was limited to tumor size and capsule invasion, a combined model in a panel of immune markers can add accuracy in the classification of challenging thyroid follicular-derived lesions.
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Objective To investigate the effect of whole body vibration training on biomechanics and Wnt3a protein expression of the femur. Methods Forty-eight female SD rats were randomly divided into sham operation group, osteoporosis group and whole body vibration group, 16 in each group. The bone morphometric parameters were measured by Micro-CT, mechanical parameters of bone structure and materials were measured by three-point bending test, protein expression of Wnt3a and β-catenin was measured by Western blotting, and gene expression of Wnt3a, β-catenin, cyclin D1 and tcf1 was detected by qRT-PCR. ResultsCompared with sham operation group, bone mineral density (BMD), bone volume fraction (BVF), trabecular number, trabecular thickness and cortical bone thickness in osteoporosis group were decreased, and trabecular space was increased; compared with osteoporosis group, BMD, BVF, trabecular number, trabecular thickness and cortical bone thickness in whole body vibration group were increased, and trabecular space was decreased. Compared with sham operation group, the maximum load, elastic load and deflection of osteoporosis group were significantly reduced; compared with osteoporosis group, the maximum load, elastic load and deflection of whole body vibration group were significantly increased. Compared with sham operation group, the maximum stress, elastic stress, maximum strain and elastic modulus in osteoporosis group decreased significantly; compared with the osteoporosis group, the elastic stress, maximum strain and elastic modulus in whole body vibration group increased significantly. Compared with sham operation group, Wnt3a, β-catenin protein and gene expression decreased, cyclin D1, tcf1 gene expression also decreased; compared with osteoporosis group, Wnt3a, β-catenin protein and gene expression increased, cyclin D1, tcf1 gene expression increased as well. Conclusions Whole body vibration training can improve biomechanical properties of the femur and expression of Wnt3a protein in osteoporotic rats. The research findings provide laboratory reference data for the prevention and treatment of osteoporosis by whole body vibration training.
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Objective To investigate the role and mechanism of RSPO1 in osteoblasts differentiation.Methods The xCELLigence system was used to study the toxicity and role of RSPO1 on the C2C12 cells proliferation.Alkaline phosphatase (ALP) activity was measured by using a phosphatase detection kit.The expression of osteoprotegerin (OPG) was determined using enzyme-linked immunosorbent assay (ELISA).Wnt/β-catenin signaling was evaluated using the TOPflash T cell factor (TCF) luciferase reporter assay.Western blotting assay was performed to confirm the accumulation of β-catenin protein.T test was used for statistical analysis.Results RSPO1 had no effect on the C2C12 cells proliferation,and it produced no toxicity to C2C12 cells.RSPO1 alone resulted in a slight increase in the activity of ALP (2.85±0.08 vs 1.74±0.21,t=3.014,P＜0.05) and the expression of OPG (1.29±0.13 vs 1.00±0.21,t=3.348,P＜0.05),whereas the combination of RSPO1 and Wnt3A significantly amplified ALP activity (81.37±5.08 vs 1.74±0.21,t=31.31,P＜0.01) and OPG protein expression (5.26±0.60 vs 1.00±0.21,t=6.99,P＜0.01).RSPO1 synergized with Wnt3A to activate TCF activity and induce accumulation of β-catenin (3.28±0.18 vs 1.00±0.21,t=10.94,P＜0.05).However,RSPO1 alone had no effect on the TCF activity and β-catenin accumulation (1.25±0.08 vs 1.00±0.21,t=2.225,P＞0.05).Conclusion Our study has revealed that RSPO1 synergized with Wnt3A in activating Wnt/β-catenin signaling pathway to induce osteoblasts differentiation,which demonstrate the therapeutic potential of RSPO1 for RA.