Melatonin protects bone marrow mesenchymal stem cells against iron overload‐induced aberrant differentiation and senescence

Abstract

Bone marrow mesenchymal stem cells (BMSCs) are an expandable population of stem cells which can differentiate into osteoblasts, chondrocytes and adipocytes. Dysfunction of BMSCs in response to pathological stimuli contributes to bone diseases. Melatonin, a hormone secreted from pineal gland, has been proved to be an important mediator in bone formation and mineralization. The aim of this study was to investigate whether melatonin protected against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Here, we found that iron overload induced by ferric ammonium citrate (FAC) caused irregularly morphological changes and markedly reduced the viability in BMSCs. Consistently, osteogenic differentiation of BMSCs was significantly inhibited by iron overload, but melatonin treatment rescued osteogenic differentiation of BMSCs. Furthermore, exposure to FAC led to the senescence in BMSCs, which was attenuated by melatonin as well. Meanwhile, melatonin was able to counter the reduction in cell proliferation by iron overload in BMSCs. In addition, protective effects of melatonin on iron overload-induced dysfunction of BMSCs were abolished by its inhibitor luzindole. Also, melatonin protected BMSCs against iron overload-induced ROS accumulation and membrane potential depolarization. Further study uncovered that melatonin inhibited the upregulation of p53, ERK and p38 protein expressions in BMSCs with iron overload. Collectively, melatonin plays a protective role in iron overload-induced osteogenic differentiation dysfunction and senescence through blocking ROS accumulation and p53/ERK/p38 activation.

Melatonin suppresses senescence‐derived mitochondrial dysfunction in mesenchymal stem cells via the HSPA1L–mitophagy pathway

“…Melatonin rescues oxidative stress‐induced premature senescence in MSCs through attenuation of p‐p38, inhibition of p16 INK4α , and augmentation of SIRT1 (Zhou et al, ). It also prevents aberrant differentiation and senescence of MSCs from iron imbalance by inhibiting ROS accumulation and membrane potential depolarization through down‐regulation of p53, ERK, and p38 (Yang et al, ). Melatonin also suppresses CKD‐associated senescence in MSCs through upregulation of PrP C (Han et al, ).…”

Effects of Blue Light Emitting Diode Irradiation On the Proliferation, Apoptosis and Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells

“…It has been demonstrated that some specific proteins [31][32][33], miRNAs [34,35] and molecules [36][37][38] are involved in the regulation of osteogenic differentiation in BMSCs. These findings suggested that osteogenic differentiation is a complicated multifactorial process.…”

Regulation effects of melatonin on bone marrow mesenchymal stem cell differentiation

“…Recently, studies have demonstrated that melatonin markedly rescues the osteogenic differentiation of BMSCs, that is, melatonin impaired the senescence of BMSCs caused by iron overload and prevented the consequent reduction of cell proliferation (Anwar, Mahfouz, & Sayed, ; Hernandez‐Plata et al, ; Lai, Jin, Tang, & Lu, ; Vriend & Reiter, ; F. Wang et al, ; Y. Yang et al, ; F. Yang, Li, et al, ; F. Yang, Yang, et al, ). Also, F. Yang, Yang, et al () investigated whether melatonin protects the dysfunction of BMSCs induced by iron overload and further explored the relevant underlying mechanisms. The results of this study have indicated that osteogenic differentiation of BMSCs was significantly inhibited by iron overload, but melatonin treatment could rescue osteogenic differentiation of BMSCs.…”