miR-125a-5p in astrocytes attenuates peripheral neuropathy in type 2 diabetic mice through targeting TRAF6.

INTRODUCTION: Elimination or blocking of astrocytes could ameliorate neuropathic pain in animal models. MiR-125a-5p, expressed in astrocyte derived extracellular vesicles, could mediate astrocyte function to regulate neuron communication. However, the role of miR-125a-5p in DPN (diabetic peripheral neuropathy) remains elusive. MATERIALS AND METHODS: Type 2 diabetic mouse (db/db) was used as DPN model, which was confirmed by detection of body weight, blood glucose, mechanical allodynia, thermal hyperalgesia, glial fibrillary acidic protein (GFAP) and monocyte chemoattractant protein-1 (MCP-1). Astrocyte was isolated from db/db mouse and then subjected to high glucose treatment. The expression of miR-125a-5p in db/db mice and high glucose-induced astrocytes was examined by qRT-PCR analysis. Downstream target of miR-125a-5p was clarified by luciferase reporter assay. Tail vein injection of miR-125a-5p mimic into db/db mice was then performed to investigate role of miR-125a-5p on DPN. RESULTS: Type 2 diabetic mice showed higher body weight and blood glucose than normal db/m mice. Thermal hyperalgesia and mechanical allodynia were decreased in db/db mouse compared with db/m mouse, while GFAP and MCP-1 were increased in db/db mouse. High glucose treatment enhanced the protein expression of GFAP and MCP-1 in astrocytes. Sciatic nerve tissues in db/db mice and high glucose-induced astrocytes exhibited a decrease in miR-125a-5p. Systemic administration of miR-125a-5p mimic increased mechanical allodynia and thermal hyperalgesia, whereas it decreased GFAP and MCP-1. TRAF6 (tumor necrosis factor receptor associated factor 6) was validated as target of miR-125a-5p. CONCLUSION: MiR-125a-5p in astrocytes attenuated DPN in db/db mice by up-regulation of TRAF6, which indicated the potential therapeutic effect.

Circular RNA mmu_circ_0001598 Contributes to IL-1ß-Induced Osteoarthritis Progression by Regulating miR-127-3p.

Osteoarthritis (OA), a chronic disease characterized by articular cartilage degeneration, is a leading cause of disability and pain worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. In this study, we found that circ_0001598 was significantly upregulated in chondrocytes treated with IL-1ß and in cartilage tissue from mice with severed anterior cruciate ligament surgery (ACLT) induced OA models. Interference with circ_0001598 in vitro restored IL-1ß-induced chondrocyte proliferation and apoptosis. Silencing circ_0001598 significantly alleviated ACLT-induced OA in mice. Mechanistically, knockdown of circ_0001598 affected chondrocyte proliferation, apoptosis, and matrix degradation by regulating miR-127-3p. Taken together, our results demonstrate the fundamental role of circ_0001598 and provide new ideas for the prevention and treatment of osteoarthritis.

miR-125a-5p in astrocytes attenuates peripheral neuropathy in type 2 diabetic mice through targeting TRAF6.

INTRODUCTION: Elimination or blocking of astrocytes could ameliorate neuropathic pain in animal models. MiR-125a-5p, expressed in astrocyte derived extracellular vesicles, could mediate astrocyte function to regulate neuron communication. However, the role of miR-125a-5p in DPN (diabetic peripheral neuropathy) remains elusive. MATERIALS AND METHODS: Type 2 diabetic mouse (db/db) was used as DPN model, which was confirmed by detection of body weight, blood glucose, mechanical allodynia, thermal hyperalgesia, glial fibrillary acidic protein (GFAP) and monocyte chemoattractant protein-1 (MCP-1). Astrocyte was isolated from db/db mouse and then subjected to high glucose treatment. The expression of miR-125a-5p in db/db mice and high glucose-induced astrocytes was examined by qRT-PCR analysis. Downstream target of miR-125a-5p was clarified by luciferase reporter assay. Tail vein injection of miR-125a-5p mimic into db/db mice was then performed to investigate role of miR-125a-5p on DPN. RESULTS: Type 2 diabetic mice showed higher body weight and blood glucose than normal db/m mice. Thermal hyperalgesia and mechanical allodynia were decreased in db/db mouse compared with db/m mouse, while GFAP and MCP-1 were increased in db/db mouse. High glucose treatment enhanced the protein expression of GFAP and MCP-1 in astrocytes. Sciatic nerve tissues in db/db mice and high glucose-induced astrocytes exhibited a decrease in miR-125a-5p. Systemic administration of miR-125a-5p mimic increased mechanical allodynia and thermal hyperalgesia, whereas it decreased GFAP and MCP-1. TRAF6 (tumor necrosis factor receptor associated factor 6) was validated as target of miR-125a-5p. CONCLUSION: MiR-125a-5p in astrocytes attenuated DPN in db/db mice by up-regulation of TRAF6, which indicated the potential therapeutic effect.