Melatonin suppresses autophagy in type 2 diabetic osteoporosis

Abstract

Type 2 diabetes mellitus is often complicated by osteoporosis, a process which may involve osteoblast autophagy. As melatonin suppresses autophagy under certain conditions, we its investigated the effects on bone autophagy during diabetes. We first assessed different body parameters in a diabetic rat model treated with various concentrations of melatonin. Dynamic biomechanicalmeasurements, bone organization hard slice dyeing and micro-CT were used to observe the rat bone microstructure, and immunohistochemistry was used to determine levels of autophagy biomarkers. We also performed in vitro experiments on human fetal osteoblastic (hFOB1.19) cells cultured with high glucose, different concentrations of melatonin, and ERK pathway inhibitors. And we used Western blotting and immunofluorescence to measure the extent of osteogenesis and autophagy. We found that melatonin improved the bone microstructure in our rat diabetes model and reduced the level of autophagy(50 mg/kg was better than 100 mg/kg). Melatonin also enhanced osteogenesis and suppressed autophagy in osteoblasts cultured at high glucose levels (10 μM was better than 1 mM). This suggests melatonin may reduce the level of autophagy in osteoblasts and delay diabetes-induced osteoporosis by inhibiting the ERK signaling pathway.

Melatonin up‐regulates bone marrow mesenchymal stem cells osteogenic action but suppresses their mediated osteoclastogenesis via MT2‐inactivated NF‐κB pathway

“…Many studies have suggested that an excessive dose (1–100 μM) of melatonin could alleviate foreigner antigen‐induced negative nonspecific responses and inflammatory cytokines, including TNF‐α and IL‐1β, which helped to inhibit the acceleration of bone loss (Lian et al, ; Liu et al, ; Ping et al, ). However, Zhang et al found that a lower concentration of melatonin played a more beneficial role (50 mg·kg −1 was better than 100 mg·kg −1 ) in improving bone microstructure in type 2 diabetic osteoporosis rats by regulating bone immunity (Zhang et al, ). Our work confirmed that the anti‐inflammatory effect of melatonin in osteoporotic mice functioned in a concentration‐dependent manner by suppressing serum TNF‐α (Figure f).…”

Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway

“…Melatonin has been documented to regulate autophagy in various cell types; however, its effect on EPCs was not uniform. Melatonin was reported to promote autophagy in diabetic cardiomyopathy, peripheral neuropathy, and to suppress autophagy in type 2 diabetic osteoporosis . However, how melatonin modulates autophagy in EPCs is still unclear: studies in articular chondrocytes have not shown that melatonin may regulate autophagy.…”

Melatonin: Another avenue for treating osteoporosis?

“…Melatonin also enhances osteogenesis and suppresses autophagy in osteoblasts cultured with high glucose levels (10 μmol/L was better than 1 mmol/L). This suggests that melatonin may lower the level of autophagy in osteoblasts and delay diabetes‐induced osteoporosis by inhibiting the ERK signaling pathway . Trabecular thickness, trabecular area, and cortical thickness in rats showed a remarkable decrease after ovariectomy.…”

“…This suggests that melatonin may lower the level of autophagy in osteoblasts and delay diabetes-induced osteoporosis by inhibiting the ERK signaling pathway. 117 Trabecular thickness, trabecular area, and cortical thickness in rats showed a remarkable decrease after ovariectomy. However, administration of melatonin improved these indices.…”