The Potential of Exosomes for Osteoporosis Treatment: A Review.

As a continuous process comprising bone resorption and formation, bone remodeling, plays an essential role in maintaining the balance of bone metabolism. One type of metabolic osteopathy is osteoporosis, which is defined by low bone mass and deteriorating bone microstructure. Osteoporosis patients are more likely to experience frequent osteoporotic fractures, which makes osteoporosis prevention and treatment crucial. A growing body of research has revealed that exosomes, which are homogenous vesicles released by most cell types, play a major role in mediating a number of pathophysiological processes, including osteoporosis. Exosomes may act as a mediator in cell-to-cell communication and offer a fresh perspective on information sharing. This review discusses the characteristics of exosomes and outlines the exosomes' underlying mechanism that contributes to the onset of osteoporosis. Recent years have seen a rise in interest in the role of exosomes in osteoporosis, which has given rise to innovative therapeutic approaches for the disease prevention and management.

Long noncoding RNA protein-disulfide isomerase-associated 3 regulated high glucose-induced podocyte apoptosis in diabetic nephropathy through targeting miR-139-3p.

BACKGROUND: Podocyte apoptosis plays a vital role in proteinuria pathogenesis in diabetic nephropathy (DN). The regulatory relationship between long noncoding RNAs (lncRNAs) and podocyte apoptosis has recently become another research hot spot in the DN field. AIM: To investigate whether lncRNA protein-disulfide isomerase-associated 3 (Pdia3) could regulate podocyte apoptosis through miR-139-3p and revealed the underlying mechanism. METHODS: Using normal glucose or high glucose (HG)-cultured podocytes, the cellular functions and exact mechanisms underlying the regulatory effects of lncRNA Pdia3 on podocyte apoptosis and endoplasmic reticulum stress (ERS) were explored. LncRNA Pdia3 and miR-139-3p expression were measured through quantitative real-time polymerase chain reaction. Relative cell viability was detected through the cell counting kit-8 colorimetric assay. The podocyte apoptosis rate in each group was measured through flow cytometry. The interaction between lncRNA Pdia3 and miR-139-3p was examined through the dual luciferase reporter assay. Finally, western blotting was performed to detect the effect of lncRNA Pdia3 on podocyte apoptosis and ERS via miR-139-3p. RESULTS: The expression of lncRNA Pdia3 was significantly downregulated in HG-cultured podocytes. Next, lncRNA Pdia3 was involved in HG-induced podocyte apoptosis. Furthermore, the dual luciferase reporter assay confirmed the direct interaction between lncRNA Pdia3 and miR-139-3p. LncRNA Pdia3 overexpression attenuated podocyte apoptosis and ERS through miR-139-3p in HG-cultured podocytes. CONCLUSION: Taken together, this study demonstrated that lncRNA Pdia3 overexpression could attenuate HG-induced podocyte apoptosis and ERS by acting as a competing endogenous RNA of miR-139-3p, which might provide a potential therapeutic target for DN.

Long noncoding RNA Glis2 regulates podocyte mitochondrial dysfunction and apoptosis in diabetic nephropathy via sponging miR-328-5p.

Podocyte apoptosis exerts a crucial role in the pathogenesis of DN. Recently, long noncoding RNAs (lncRNAs) have been gradually identified to be functional in a variety of different mechanisms associated with podocyte apoptosis. This study aimed to investigate whether lncRNA Glis2 could regulate podocyte apoptosis in DN and uncover the underlying mechanism. The apoptosis rate was detected by flow cytometry. Mitochondrial membrane potential (ΔΨM) was measured using JC-1 staining. Mitochondrial morphology was detected by MitoTracker Deep Red staining. Then, the histopathological and ultrastructure changes of renal tissues in diabetic mice were observed using periodic acid-Schiff (PAS) staining and transmission electron microscopy. We found that lncRNA Glis2 was significantly downregulated in high-glucose cultured podocytes and renal tissues of db/db mice. LncRNA Glis2 overexpression was found to alleviate podocyte mitochondrial dysfunction and apoptosis. The direct interaction between lncRNA Glis2 and miR-328-5p was confirmed by dual luciferase reporter assay. Furthermore, lncRNA Glis2 overexpression alleviated podocyte apoptosis in diabetic mice. Taken together, this study demonstrated that lncRNA Glis2, acting as a competing endogenous RNA (ceRNA) of miRNA-328-5p, regulated Sirt1-mediated mitochondrial dysfunction and podocyte apoptosis in DN.

The potential mechanism of the microbiota-gut-bone axis in osteoporosis: a review.

Osteoporosis is the prevalent metabolic bone disease characterized by a decrease in bone quantity and/or quality and an increase in skeletal fragility, which increases susceptibility to fractures. Osteoporotic fractures severely affect the patients' quality of life and mortality. A plethora of evidences have suggested that the alterations in gut microbiome are associated with the changes in bone mass and microstructure. We summarized pre-clinical and clinical studies to elucidate the underlying mechanism of gut microbiota in osteoporosis. Probiotics, prebiotics, and traditional Chinese medicine may reverse the gut microbiota dysbiosis and consequently improve bone metabolism. However, the causality of gut microbiota on bone metabolism need to be investigated more in depth. In the present review, we focused on the potential mechanism of the microbiota-gut-bone axis and the positive therapeutic effect of probiotics, prebiotics, and traditional Chinese medicine on osteoporosis. Overall, the current scientific literatures support that the gut microbiota may be a novel therapeutic target in treatment of osteoporosis and fracture prevention.

The potential role of lncRNAs in osteoporosis.

Osteoporosis is a common bone disease characterized by low bone mass and deterioration of bone microstructure, which predisposes to higher risks of bone fragility and bone fracture. Long non-coding RNAs (lncRNAs) are a class of RNAs with a length of > 200 nucleotides without protein-coding function, which control the expression of genes and affect multiple biological processes. Accumulating evidence suggests that lncRNAs are widely involved in the molecular mechanisms of osteoporosis. This review aims to summarize the function and underlying mechanism of lncRNAs involved in the development of osteoporosis, and how it contributes to osteoblast and osteoclast function. This knowledge will shed new light on the modulation and potential treatment of osteoporosis.

The potential role of lncRNAs in diabetes and diabetic microvascular complications.

Long noncoding RNAs (lncRNAs) are a group of noncoding RNAs that are longer than 200 nucleotides without protein-coding potential. Becasuse of which these RNAs have no significant protein-coding potential, they were initially considered as "junk-products" of transcription without biological meaning. Nevertheless, recent research advancements have shown that lncRNAs are involved in many physiological processes such as cell cycle regulation, cell apoptosis and survival, cancer migration and metabolism. This review described the function of lncRNAs and the potential underlying mechanism involved in diabetes and diabetic microvascular complications. The roles of lncRNAs in the pathogenesis of type 2 diabetes mellitus have only recently been recognized, involving hepatic glucose production and insulin resistance. We further investigated the mechanisms of lncRNAs in diabetic nephropathy (DN), including the roles of lncRNAs in mesangial cells (MCs) proliferation and fibrosis, inflammatory processes, extracellular matrix accumulation in the glomeruli and tubular injury. We also discussed the potential mechanism of lncRNAs in diabetic retinopathy (DR), including aberrant neovascularization and neuronal dysfunction. This review summarized the current knowledge of the functions and underlying mechanisms of lncRNAs in type 2 diabetes mellitus and related renal and retinal complications. Accumulating evidence suggests the potential of lncRNAs as therapeutic targets for clinical applications in the management of diabetes.

ERRFI1 Inhibits Proliferation and Inflammation of Nucleus Pulposus and Is Negatively Regulated by miR-2355-5p in Intervertebral Disc Degeneration.

STUDY DESIGN: In vivo and in vitro studies of the role of miR-2355-5p and its possible targets in intervertebral disc degeneration (IVDD). OBJECTIVE: To elucidate the regulatory role of miR-2355-5p in IVDD and the underlying mechanisms. SUMMARY OF BACKGROUND DATA: IVDD, which is caused by multiple factors, is the main cause of lower back pain with or without extremity pain. However, the underlying cellular mechanisms of IVDD pathogenesis are not well elucidated. Cell hyper-proliferation, inflammation, and epidermal growth factor receptor activation have been implicated in IVDD. Up-regulated miR-2355-5p level was identified to associate with IVDD. ERRFI1 (the product of mitogen-inducible gene 6 [MIG6]) was known to inhibit epidermal growth factor receptor activation. METHODS: We monitored the expression of miR-2355-5p and ERRFI1 in IVDD tissues and lipopolysaccharides (LPS)-treated nucleus pulposus (NP) cells. We explored the effects of ERFFI1 on NP cells proliferation and LPS-induced pro-inflammatory cytokines production. We searched the targets of miR-2355-5p and explored the effects of miR-2355-5p on NP cells proliferation and cytokines production. RESULTS: We identified the up-regulation of miR-2355-5p and down-regulation of ERFFI1 in IVDD samples and LPS-treated NP cells. ERFFI1 inhibited NP cells proliferation and LPS-induced pro-inflammatory cytokine production. MiR-2355-5p targeted ERFFI1 and negatively regulated ERFFI1 expression. MiR-2355-5p regulated IVDD by targeting ERFFI1. CONCLUSION: MiR-2355-5p negatively regulated ERFFI1 and prevented the effects of ERRFI1 on inhibiting NP cells proliferation and inflammation. LEVEL OF EVIDENCE: N/A.

Rapidly progressive rhino-orbito-cerebral mucormycosis in a patient with type 2 diabetes: A case report.

With the ongoing economic development, lifestyle changes and an aging population, diabetes mellitus has be come one of the most prevalent chronic diseases in the world. Rhino-orbito-cerebral (ROC) mucormycosis is a rare, acute and angioinvasive fungal infection that can be fatal. Mucormycosis occurs exclusively in immunocompromised patients with diabetes mellitus and other types of immunodeficiency and has three subtypes: Rhino-maxillary, rhino-orbital and ROC mucormycosis. The present study reported on a case of ROC mucormycosis in a patient with diabetic ketoacidosis. In the present case, the pathogen afflicted all of the above organs, including the left eye, nasal cavity, hard palate and cerebrum.