RESUMO
Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and bone quality and increased bone porosity, which increase the risk of bone fracture. Inflammation, one of the important mechanisms related to aging, is associated with osteoporosis. Treatment with anti-inflammatory agents is effective for alleviating senile osteoporosis. Alginate oligosaccharide (AOS) can prevent and treat diseases related to inflammation, oxidative stress, and immunity. This study evaluates the effect of AOS on osteoporosis and investigates the underlying mechanism. Osteoporosis model was induced by D-galactose (D-gal) (200 mg kg-1 day-1 ) for eight weeks. Three groups were administered via AOS (50, 100, and 150 mg kg-1 day-1 ) for four weeks, while a control group received sterile water (5 ml kg-1 day-1 ) for 8 weeks. The results showed that AOS improved bone density and bone microstructure in D-gal-induced osteoporosis mice. AOS inhibited osteoclast proliferation, probably through the suppression of receptor activator of nuclear factor-kappa B ligand (RANKL)-associated nuclear factor kappa B (NF-κB) and c-Fos signaling pathway. AOS also increased osteoprotegerin (OPG) expression and competitively inhibited the binding between RANK and RANKL in senile osteoporosis. Further, AOS decreased the secretion of serum osteocalcin and reduced bone conversion. Together, these results demonstrate the anti-osteoporosis activity of AOS in mice with osteoporosis.
Assuntos
Alginatos/química , Galactose/farmacologia , Oligossacarídeos/química , Oligossacarídeos/uso terapêutico , Osteoporose/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Animais , Densidade Óssea/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Oligossacarídeos/farmacologia , Osteoporose/patologia , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Osteoporosis (OP), a common metabolic bone disease, is accompanied by reduced bone mass, bone mineral density (BMD), as well as microstructure destruction of bone. Previously, microRNA-196a-2 (miR-196a-2) and miR-196a-3p were reported for its involvement in BMD. Herein, this study set out to identify the functional relevance of miR-196a in osteogenic differentiation in osteoporotic mice and explore the associated mechanism by establishing an OP mouse model. Guanine nucleotide binding protein, alpha stimulating (GNAS) was verified as a target gene of miR-196a, which was decreased in OP mice. Furthermore, the bone marrow stromal cells (BMSCs) were then extracted from OP mice and treated with miR-196 mimic/inhibitor or small interfering RNA against GNAS to investigate miR-196a interaction with GNAS and the Hedgehog signaling pathway. BMSCs in OP mice transfected with miR-196a mimic or si-GNAS displayed the elevated expression of Smo, ALP, Runx2, and OPN, as well as bone gla protein and tartrate-resistant acid phosphatase, elevated ALP vitality and bone formation ability as well as reduced expression of GNAS and PTCH. Taken conjointly, overexpression of miR-196a repressed GNAS expression by activating the Hedgehog signaling pathway, thus promoting osteogenic differentiation in mice with OP.
Assuntos
Diferenciação Celular/fisiologia , Proteínas Hedgehog/metabolismo , MicroRNAs/metabolismo , Osteogênese/fisiologia , Osteoporose/metabolismo , Animais , Diferenciação Celular/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas Hedgehog/genética , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Osteogênese/genética , Osteoporose/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: To analyze the relation of HBV infection with clinical characteristics and prognosis in NHL patients, so as to explore the significance of HBV detection. METHODS: Sixty-eight NHL patients from December 2013 to December 2016 were enrolled in NHL group and 136 patients with other malignancies were chosen in control group, the detectable rate of HBV was compared between 2 groups. The correlation of HBV infection with sex, age, stage, cell origin, expression of P53 and BCL-2 in NHL patients was analyzed. The prognosis-related factors in NHL patients were also analyzed. RESULTS: The infection rate of HBV in NHL group was 51.47%(35/68), that in control group was 15.44% (21/136), and the difference was statistically significant(χ2=27.768,P<0.05). HBV infection correlated with cell origins and expression of BCL-2 in NHL patients(P<0.05). The prognosis of NHL patients demonstrated no correlation with sex, age, cell origins and HBV infection (P>0.05), while the prognosis was significantly related with stage, expression of P53 and BCL-2(P<0.05). CONCLUSION: HBV infection correlates with BCL-2 expression level of NHL patients, and shows influence on the prognosis of patients.