Vascular endothelial cells-derived exosomes synergize with curcumin to prevent osteoporosis development.

Osteoporosis has gradually become a major public health problem. Further elucidation of the pathophysiological mechanisms that induce osteoporosis and identification of more effective therapeutic targets will have important clinical significance. Experiments in vitro on bone marrow stem cells (BMSCs) subjected to osteogenic and adipogenic differentiation and in vivo on surgical bilateral ovariectomy (OVX) mouse models revealed that exosomes of vascular endothelial cells (EC-EXOs) can promote osteogenic differentiation of BMSCs and inhibit BMSC adipogenic differentiation through miR-3p-975_4191. Both miR-3p-975_4191 and curcumin can target tumor necrosis factor (TNF) and act synergistically to regulate BMSCs fate differentiation and delay the progression of osteoporosis. Our findings suggest that EC-EXOs may exert a synergistic effect with curcumin in reversing the progression of osteoporosis by targeting TNF via miR-3p-975_4191. Our study may provide therapeutic options and potential therapeutic targets for osteoporosis and thus has important clinical implications.

Exosome-derived miR-5p-72106_14 in vascular endothelial cells regulates fate determination of BMSCs.

Vascular endothelial cells have recently been shown to be associated with osteogenic activity. However, the mechanism of vascular endothelial cells promoting osteogenesis is unclear. Here, we found that exosomes secreted from human microvascular endothelial cells (HMEC-1) promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and inhibited adipogenic differentiation. Aged and ovariectomy mice treated with exosomes showed increased bone formation and decreased lipid accumulation in the bone marrow cavity. Additionally, we screened out novel exosomal miR-5p-72106_14 by miRNA-seq and confirmed that miR-5p-72106_14 promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs by inhibiting STAT1. Our results suggest that vascular endothelial cell-derived exosomes are involved in BMSC differentiation and exosomal miR-5p-72106_14 is a major factor in regulating fate determination of BMSCs.

Melatonin or vitamin C attenuates lead acetate-induced testicular oxidative and inflammatory damage in mice by inhibiting oxidative stress mediated NF-κB signaling.

Lead (Pb) acts as an environmental endocrine disruptor and has negative effects in animals; excessive accumulation of lead causes reproductive dysfunction in male animals. Oxidative stress plays a vital role in Pb-induced injury. However, the mechanisms underlying chronic testicular toxicity of Pb remain unclear. In this study, we aimed to determine the effects of lead acetate on reproductive function in male mice, identify the underlying mechanisms, and test counter measures to alleviate the toxic effects. Male mice were dosed with lead acetate (500 mg/L) in free drinking water for 12 weeks, and administered melatonin (5 mg/kg) or vitamin C (500 mg/kg) by intraperitoneal injection. Blood from the eyeball, testicles, and sperm from the caudal epididymis were collected after 12 weeks and analyzed. Pb exposure reduced sperm count and motility, increased sperm malformation (P < 0.01), disrupted testicular morphology and structure, and decreased the expression of steroid hormone synthesis-related enzymes and serum testosterone concentration (P < 0.01). Pb also increased the number of inflammatory cells and the levels of the pro-inflammatory cytokines TNF-α and IL-6 (P < 0.01), and activated NF-κB signaling. Furthermore, the ROS yield and oxidation indicators LPO and MDA were significantly increased (P < 0.01), and the antioxidant indicators T-AOC, SOD, and GSH were significantly reduced (P < 0.01). Treatment with melatonin or vitamin C reversed the effects of lead acetate; vitamin C was more effective in restoring SOD activity (P < 0.01) and enhancing ZO-1 protein levels (P < 0.01). Thus, long-term exposure to lead acetate at low concentrations could adversely affect sperm quality and induce inflammatory damage by oxidative stress mediated NF-κB signaling. Vitamin C could act as a protective agent and improve reproductive dysfunction in male animals after lead accumulation.

Role of Exosomal Non-Coding RNAs in Bone-Related Diseases.

Bone-related diseases seriously affect the lives of patients and carry a heavy economic burden on society. Treatment methods cannot meet the diverse clinical needs of affected patients. Exosomes participate in the occurrence and development of many diseases through intercellular communication, including bone-related diseases. Studies have shown that exosomes can take-up and "package" non-coding RNAs and "deliver" them to recipient cells, thereby regulating the function of recipient cells. The exosomal non-coding RNAs secreted by osteoblasts, osteoclasts, chondrocytes, and other cells are involved in the regulation of bone-related diseases by inhibiting osteoclasts, enhancing chondrocyte activity and promoting angiogenesis. Here, we summarize the role and therapeutic potential of exosomal non-coding RNAs in the bone-related diseases osteoporosis, osteoarthritis, and bone-fracture healing, and discuss the clinical application of exosomes in patients with bone-related diseases.