RESUMO
Abstract Purpose: To investigate inhibitory effect of Astragalus polysaccharide (APS) on osteoporosis in ovariectomized rats by regulating FoxO3a/Wnt2 signaling pathway. Methods: Postmenopausal osteoporosis (PMOP) animal model was developed by excising the bilateral ovaries of rats. The model rats were administered with APS (200 mg/kg, 400 mg/kg, 800 mg/kg) by intragastric administration once daily for 12 weeks. Bone density, bone metabolism index and oxidative stress index were measured in all groups. Furthermore, the regulation of APS of FoxO3a / Wnt2 signaling pathway was observed. Results: APS has an estrogen-like effect, which can increase bone mass, lower serum ALP and BGP values, increase blood calcium content, and increase bone density of the femur and vertebrae in rats. At the same time, APS can increase the bone mineral content of the femur, increase the maximum stress, maximum load and elastic modulus of the ovariectomized rats, improve oxidative stress in rats by increasing the gene expression of β-catenin and Wnt2 mRNA and inhibiting the gene expression of FoxO3a mRNA. Conclusion: Astragalus polysaccharide can effectively alleviate oxidative stress-mediated osteoporosis in ovariectomized rats, which may be related to its regulation of FoxO3a/Wnt2/β-catenin pathway.
Assuntos
Animais , Feminino , Osteoporose/tratamento farmacológico , Polissacarídeos/farmacologia , Astrágalo/química , Via de Sinalização Wnt/efeitos dos fármacos , Proteína Forkhead Box O3/efeitos dos fármacos , Osteoporose/metabolismo , Valores de Referência , Ovariectomia , Distribuição Aleatória , Densidade Óssea/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Reprodutibilidade dos Testes , Resultado do Tratamento , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Proteína Wnt2/análise , Proteína Wnt2/efeitos dos fármacos , beta Catenina/análise , beta Catenina/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/análise , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Via de Sinalização Wnt/fisiologia , Proteína Forkhead Box O3/análiseRESUMO
<p><b>OBJECTIVE</b>To study the role of abnormally activated Wnt/β-catenin signal pathway in the pathogenesis of scleroderma (SD) and its association with the clinical classification of SD.</p><p><b>METHODS</b>The expression and distribution of Wnt 2, Wnt 3a, and β-catenin in the skin lesions of 45 SD patients, including 25 with systemic sclerosis (SSc) and 20 with localized scleroderma (LSc), were detected with SP immunohistochemistry, using 20 samples from healthy skin tissues as normal control.</p><p><b>RESULTS</b>In the dermis and epidermis of the SD skin lesions, Wnt 2 and Wnt 3a were located in the cytoplasm and cell nuclei, respectively; β-catenin was distributed in the nuclei of dermal fibroblast-like cells, glandular epithelium cells and infiltrating lymphocytes, and on the cell membrane in normal and a part of the affected epidermis. The skin lesions of SD patients showed obviously increased staining intensity of cytoplasmic Wnt 2, nuclear Wnt 3a and β-catenin, but markedly lowered cell membrane staining of β-catenin than normal skins (P<0.01). Both Wnt 2 and Wnt 3a were positively correlated with nuclear β-catenin deposition (r=0.663 and 0.654, P<0.01) and negatively with cell membrane β-catenin staining (r=-0.532 and -0.529, P<0.01). No significant difference was found in the staining intensities of the 3 proteins between SSc and LSc (P>0.05).</p><p><b>CONCLUSION</b>Abnormal activation of Wnt/β-catenin pathway occurs in the skin lesions of SD patients, which may play an important role in the pathogenesis of SD. SSc and LSc represent the two opposite ends of the SD spectrum rather than two separate diseases.</p>