Melatonin prevents cadmium‐induced bone damage: First evidence on an improved osteogenic/adipogenic differentiation balance of mesenchymal stem cells as underlying mechanism

Abstract

Melatonin (MLT) plays a role in preserving bone health, a function that may depend on homeostatic effects on both mature osteoblasts and mesenchymal stem cells (MSCs) of the bone tissue. In this study, these functions of MLT have been investigated in rat bone (femur) and in human adipose MSC (hMSC) during chronic exposure to low‐grade cadmium (Cd) toxicity, a serious public health concern. The in vivo findings demonstrate that MLT protects against Cd‐induced bone metabolism disruption and accumulation of bone marrow adipocytes, a cue of impaired osteogenic potential of skeletal MSC niches. This latter symptom was recapitulated in hMSCs in which Cd toxicity stimulated adipogenic differentiation. MLT was found to rescue, at least in part, the osteogenic differentiation properties of these cells. This study reports on a new bone cytoprotection function of MLT pertinent to Cd toxicity and its interfering effect on skeletal MSC differentiation properties that is worth investigating for its possible impact on human bone pathophysiology.

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

“…Although the positive effect of melatonin on the osteogenic differentiation of human mesenchymal stem cells has been investigated and affirmed in several studies (Knani, Bartolini et al, ; Lian, Wu et al, 2016), interspecies interpretation and application from mice to humans should be done with great care, and our work further consolidated the perspective of the bone protection effects of melatonin on osteoporosis and we have determine more completely mechanisms involved. In conclusion, our study shows that melatonin exerts dual anti‐inflammatory and bone‐protective effects in osteoporotic mice.…”

“…First, the origins of cells were different, the bone marrow mesenchymal stem cells we used were isolated from C57BL/6J mice, and the high sensitivity of these primary cells enabled them to detect any small changes. Therefore, as Knani et al reported, low‐dose melatonin was sufficient to affect the osteogenic/adipogenic differentiation balance in primary human adipose mesenchymal stem cells (Knani, Bartolini, et al, ). Second, ethanol was needed to dissolve the melatonin powder, but a higher concentrations of melatonin required more ethanol, which would actually inhibit cell proliferation (Figure S1B).…”

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction

“…Total ROS production was measured by immunofluorescence with a 2 ,7 -dichlorofluorescin diacetate Cellular ROS Detection Assay Kit (ab113851; Abcam, Cambridge, MA, United States) according to the manufacturer's instructions (Quispe et al, 2019). Mitochondria-derived ROS levels in cardiomyocytes were measured using a mitochondrial superoxide indicator (MitoSOX TM Red, M36008; Thermo Fisher Scientific) through immunofluorescence as previously described (Knani et al, 2019).…”

Cadmium‐induced toxicity increases prolyl endopeptidase (PREP) expression in the rat testis

“…Tobacco smoking is a major source of Cd intake, a cigarette contains 5 mg of this metal, which could lead to significantly 4–5 times higher levels of Cd in smokers’ blood than that of non‐smokers (Djuric et al, 2015; Takiguchi & Yoshihara, 2006). Generally, the Cd poisoning is the result of a chronic exposure, which is mainly reflected to bone (Järup, Alfvén, Persson, Toss and Elinder, 1998; Knani, Bartolini, et al, 2019; Knani, Venditti, et al, 2019; Xie & Sheng, 2017), kidney (Johri, Jacquillet, & Unwin, 2010; Satarug, 2018), gastrointestinal tract (Tinkov et al, 2018), lung (Ganguly, Levänen, Palmberg, Åkesson, & Lindén, 2018), and testis pathologies, whereas the latest one is the major target organ of Cd toxicity, due to its high sensitivity (Siu, Mruk, Porto, & Cheng, 2009).…”