Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy.

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.

Adipose exosomal noncoding RNAs: Roles and mechanisms in metabolic diseases.

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.

Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study.

Epigenetics regulates gene expression and has been confirmed to play a critical role in a variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism and others. The term 'epigenetics' was firstly proposed in 1942 and with the development of technologies, the exploration of epigenetics has made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, and noncoding RNA (ncRNA), which exert different effects on metabolic diseases. Genetic and non-genetic factors, including ageing, diet, and exercise, interact with epigenetics and jointly affect the formation of a phenotype. Understanding epigenetics could be applied to diagnosing and treating metabolic diseases in the clinic, including epigenetic biomarkers, epigenetic drugs, and epigenetic editing. In this review, we introduce the brief history of epigenetics as well as the milestone events since the proposal of the term 'epigenetics'. Moreover, we summarise the research methods of epigenetics and introduce four main general mechanisms of epigenetic modulation. Furthermore, we summarise epigenetic mechanisms in metabolic diseases and introduce the interaction between epigenetics and genetic or non-genetic factors. Finally, we introduce the clinical trials and applications of epigenetics in metabolic diseases.