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1.
J Nanobiotechnology ; 22(1): 361, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38910236

RESUMO

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.


Assuntos
Autofagia , Temperatura Baixa , Exossomos , Camundongos Endogâmicos C57BL , MicroRNAs , Osteogênese , Animais , Autofagia/efeitos dos fármacos , Camundongos , Exossomos/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Osteogênese/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteoporose/patologia , Diferenciação Celular/efeitos dos fármacos , Osso e Ossos/metabolismo , Feminino , Densidade Óssea , Sirolimo/farmacologia
2.
Obes Rev ; 25(6): e13740, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38571458

RESUMO

Exosomes are extracellular vesicles, measuring 40-160 nm in diameter, that are released by many cell types and tissues, including adipose tissue. Exosomes are critical mediators of intercellular communication and their contents are complex and diverse. In recent years, accumulating evidence has proved that multiple adipose tissue-derived exosomal noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in the pathogenesis of diverse metabolic diseases, such as obesity. In this narrative review, we focus on the adipose tissue-derived exosomal ncRNAs, especially exosomal miRNAs, and their dysregulation in multiple types of metabolic diseases. A deeper understanding of the role of adipose tissue-derived exosomal ncRNAs may help provide new diagnostic and treatment methods for metabolic diseases.


Assuntos
Tecido Adiposo , Exossomos , Doenças Metabólicas , RNA não Traduzido , Humanos , Exossomos/metabolismo , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Tecido Adiposo/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/fisiologia , Animais
3.
J Bone Miner Res ; 39(7): 942-955, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38624186

RESUMO

The correlation between socio-economic status (SES) and bone-related diseases garners increasing attention, prompting a bidirectional Mendelian randomization (MR) analysis in this study. Genetic data on SES indicators (average total household income before tax, years of schooling completed, and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fractures (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses and multivariable MR were performed to enhance the robustness of our findings. Higher educational attainment exhibited associations with increased eBMD (ß: .06, 95% confidence interval [CI]: 0.01-0.10, P = 7.24 × 10-3), and reduced risks of osteoporosis (OR: 0.78, 95% CI: 0.65-0.94, P = 8.49 × 10-3), spine fracture (OR: 0.76, 95% CI: 0.66-0.88, P = 2.94 × 10-4), femur fracture (OR: 0.78, 95% CI: 0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR: 0.79, 95% CI: 0.70-0.88, P = 2.05 × 10-5), foot fracture (OR: 0.78, 95% CI: 0.66-0.93, P = 5.92 × 10-3), and wrist-hand fracture (OR: 0.83, 95% CI: 0.73-0.95, P = 7.15 × 10-3). Material deprivation appeared to increase the risk of spine fracture (OR: 2.63, 95% CI: 1.43-4.85, P = 1.91 × 10-3). A higher FN-BMD level positively affected increased household income (ß: .03, 95% CI: 0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index, type 2 diabetes, smoking initiation, and frequency of alcohol intake. The MR analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings provide valuable insights for health guideline formulation and policy development.


We conducted stratified analyses to explore the causal links between socio-economic status and osteoporosis and various fractures and observed that education significantly reduced the risk of osteoporosis and lower eBMD. It also lowered the risks of fractures of spine, femur, lower leg-ankle, foot, and wrist-hand, while material deprivation exhibited positive associations with spine fracture risk. Bidirectional MR analysis showed that an elevated score of FN-BMD was associated with a higher income level. Our study shows the importance of conducting routine BMD estimations and osteoporosis screening, to enhance knowledge and awareness among individuals to promote bone health and prevent fractures.


Assuntos
Fraturas Ósseas , Análise da Randomização Mendeliana , Osteoporose , Classe Social , Humanos , Osteoporose/genética , Osteoporose/epidemiologia , Feminino , Masculino , Fraturas Ósseas/genética , Fraturas Ósseas/epidemiologia , População Branca/genética , Densidade Óssea/genética , Pessoa de Meia-Idade , Europa (Continente)/epidemiologia , Estudo de Associação Genômica Ampla
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