Melatonin rescues the mitochondrial function of bone marrow‐derived mesenchymal stem cells and improves the repair of osteoporotic bone defect in ovariectomized rats

Abstract

Osteoporotic bone defects, a severe complication of osteoporosis, are distinguished by a delayed bone healing process and poor repair quality. While bone marrow‐derived mesenchymal stem cells (BMMSCs) are the primary origin of bone‐forming osteoblasts, their mitochondrial function is impaired, leading to inadequate bone regeneration in osteoporotic patients. Melatonin is well‐known for its antioxidant properties and regulation on bone metabolism. The present study postulated that melatonin has the potential to enhance the repair of osteoporotic bone defects by restoring the mitochondrial function of BMMSCs. In vitro administration of melatonin at varying concentrations (0.01, 1, and 100 μM) demonstrated a significant dose‐dependent improvement in the mitochondrial function of BMMSCs obtained from ovariectomized rats (OVX‐BMMSCs), as indicated by an elevation in mitochondrial membrane potential, adenosine triphosphate synthesis and expression of mitochondrial respiratory chain factors. Melatonin reduced the level of mitochondrial superoxide by activating the silent information regulator type 1 (SIRT1) and its downstream antioxidant enzymes, particularly superoxide dismutase 2 (SOD2). The protective effects of melatonin were found to be nullified upon silencing of Sirt1 or Sod2, underscoring the crucial role of the SIRT1‐SOD2 axis in the melatonin‐induced enhancement of mitochondrial energy metabolism in OVX‐BMMSCs. To achieve a sustained and localized release of melatonin, silk fibroin scaffolds loaded with melatonin (SF@MT) were fabricated. The study involved the surgical creation of bilateral femur defects in OVX rats, followed by the implantation of SF@MT scaffolds. The results indicated that the application of melatonin partially restored the mitochondrial energy metabolism and osteogenic differentiation of OVX‐BMMSCs by reinstating mitochondrial redox homeostasis. These findings suggest that the localized administration of melatonin through bone implants holds potential as a therapeutic approach for addressing osteoporotic bone defects.

Favorable osteogenic activity of vericiguat doped in β-tricalcium phosphate: In vitro and in vivo studies

“…It is evident that VIT treatment led to a significant decrease in RANKL levels and an increase in SOD2, SIRT1, and OPG expression in MC3T3-E1 cells ( p < .05). Furthermore, intervention with Melatonin (MT, 1 mM, an effective antioxidant stress agent) 33 effectively mitigated the adverse effects induced by H 2 O 2 . Moreover, VIT demonstrated the ability to partially restore changes in mitochondrial membrane potential caused by H 2 O 2 intervention.…”

Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism

“…Gu et al demonstrated that MLT restores the mitochondrial energy metabolism by activating the silent information regulator type 1 (SIRT1) and its downstream antioxidant enzyme superoxide dismutase 2 (SOD2), thereby promoting osteogenic differentiation of BMSCs. 101 Tu et al also found that MLT contributes to osteogenic differentiation of BMSCs via the circ_0005753/PTBP1/TXNIP axis. 102 In addition, Wu et al revealed that MLT could reduce intracellular ROS levels and enhance antioxidant capacity of BMMs from aged mice, which inhibits RANKL-induced osteoclastogenesis, ultimately improving bone loss and deterioration of bone microstructure.…”

“…Gu et al . demonstrated that MLT restores the mitochondrial energy metabolism by activating the silent information regulator type 1 (SIRT1) and its downstream antioxidant enzyme superoxide dismutase 2 (SOD2), thereby promoting osteogenic differentiation of BMSCs 101 . Tu et al .…”

Preliminary study of the homeostatic regulation of osseointegration by nanotube topology

“…Studies have shown that most postimplant failures derive from the suppression of osteoblast function and overactivity of osteoclasts on the implant surface [ 7 ]. Therefore, dedicate control of the ratio between bone formation and resorption, ensuring a constant bone volume and maintaining bone homeostasis [ 8 ], via optimization of the biological properties of the implant is highly desirable [ 9 ].…”