Wnt4 signaling mediates protective effects of melatonin on new bone formation in an inflammatory environment

Li, Xiang; Li, Zihao; Wang, Jianru; Li, Zemin; Cui, Haowen; Dai, Guo; Chen, Siwen; Zhang, Mingliang; Zheng, Zhaomin; Zhan, Zhi-Hui; Liu, Hui

doi:10.1096/fj.201900093rr

Cited by 29 publications

(35 citation statements)

References 48 publications

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“…Melatonin plays a role in various physiological activities, serving as a gatekeeper of circadian clocks, modulating memory formation and even passing circadian timing cues from mother to infant [30,33,34]. Melatonin improves new bone formation through mediating Wnt4 signaling and increases the uptake of oxidized vitamin C via upregulating Glut1 [35,36]. In addition, melatonin protected against obesity and relative hepatic steatosis by improving lipid dysmetabolism, stimulating brown adipose tissue (BAT) browning, inhibiting epididymal adipocyte-derived exosomal resistin and attenuating inflammation in high-fat diet (HFD)-fed mice [37][38][39][40][41].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

Hong

Pan

et al. 2020

Cells

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Misalignment between natural light rhythm and modern life activities induces disruption of the circadian rhythm. It is mainly evident that light at night (LAN) interferes with the human endocrine system and contributes to the increasing rates of obesity and lipid metabolic disease. Maintaining hepatointestinal circadian homeostasis is vital for improving lipid homeostasis. Melatonin is a chronobiotic substance that plays a main role in stabilizing bodily rhythm and has shown beneficial effects in protecting against obesity. Based on the dual effect of circadian rhythm regulation and antiobesity, we tested the effect of melatonin in mice under constant light exposure. Exposure to 24-h constant light (LL) increased weight and insulin resistance compared with those of the control group (12-h light–12-h dark cycle, LD), and simultaneous supplementation in the melatonin group (LLM) ameliorated this phenotype. Constant light exposure disturbed the expression pattern of a series of transcripts, including lipid metabolism, circadian regulation and nuclear receptors in the liver. Melatonin also showed beneficial effects in improving lipid metabolism and circadian rhythm homeostasis. Furthermore, the LL group had increased absorption and digestion of lipids in the intestine as evidenced by the elevated influx of lipids in the duodenum and decrease in the efflux of lipids in the jejunum. More interestingly, melatonin ameliorated the gut microbiota dysbiosis and improved lipid efflux from the intestine. Thus, these findings offer a novel clue regarding the obesity-promoting effect attributed to LAN and suggest a possibility for obesity therapy by melatonin in which melatonin could ameliorate rhythm disorder and intestinal dysbiosis.

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Section: Introductionmentioning

confidence: 99%

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

Hong

Pan

et al. 2020

Cells

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“…Thus, promotion of bone healing by MEL could be related with one or more of the following possible mechanisms: the promotion of the osteoblast differentiation and/or activity, an increased expression of the osteoprotegerin by osteoblasts, resulting with a decreased differentiation of osteoclasts, and increased scavenging of free radicals which were generated by osteoclasts [31]. Further, and more specifically, it has been speculated that MEL interferes with bone healing in several ways: through modulation of oxidative stres [27,28,32], collagen fibril formation [19], differentiation of osteoblasts via PDGF/AKT signaling pathway [9,25,26,35,43], or activity of osteoblasts and osteoclasts via MEL-MT2 receptor pathway [9,34,41] or RANK/NF-κB signaling pathway [14,26] or Wnt/β-catenin signaling pathway [40,25,16,40]. Moreover, MEL has also been found to stimulate gene expression of BSP and other bone marker proteins including alkaline phosphate, secreted protein, osteocalcin and osteopontin [30].…”

Section: Discussionmentioning

confidence: 99%

The influence of functional pinealectomy and exogenous melatonin application on healing of a burr hole in adult rat calvaria: a histological and immunohistochemical study

Başaloğlu¹,

Turğut

Şirin

et al. 2022

Folia Morphol

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Background: Even today, repair of the cranial defects still represents a significant challenge in neurosurgery and various options have been used for their reconstruction to date. but there are very few studies investigating the effects of exogenous administration of melatonin (MEL) as an agent that promotes bone regeneration. The goal of this study was to investigate the effects of functional pinealectomy (Px) and exogenous MEL administration on the bone repair properties and surrounding connective tissue alterations in a rat calvaria model. Materials and methods:The total of 30 adult female Wistar-Albino rats was randomly divided into three groups (n = 10): control (CO) group (12 h light/12 h dark exposure), functional Px group (24 h light exposure, light-induced functional Px), and Px+MEL group (light-induced Px plus MEL, 20 mg/kg/day for 12 weeks). Critical-sized burr-hole defects (diameter = 3.0 mm) were surgically created by a single operator in the calvarium of all rats, using an electric drill. Animals in Px+MEL group received MEL 20 mg/kg/day for 12 weeks.At the end of the study, bone healing and connective tissue alterations surrounding drilled defect area in the rat calvaria were determined in hematoxylin/eosin-stained and mallory azan slices applied in anti-bone sialoprotein (BSP). Image Pro Express 4.5 program was used for histomorphometric calculation of areas of new bone and fibrotic tissue. Normality control was performed by Shapiro Wilk test. Variance homogeneities were examined by Shapiro Wilk and Levene tests; Tukey HSD test was used as a post hoc method since there was no homogeneity problem. All hypothesis tests were performed at the 0.05 significance level.Results: Histological analysis showed that the bone repair process in the Px+MEL group was similar to that of the CO group, whereas the functional Px group showed a delay.Histomorphometrically, it was found that the Px group had the largest hole diameter and the most fibrotic scar area, although no binary statistical significance was found between the CO and Px+MEL groups (p=0.910). In terms of vascularization, it was observed that the most vascular structure was found in the Px+MEL group among the scar tissue and ossification areas, while the vascularization was the least in the Px group (p < 0.001). Conclusions:Our findings revealed that bone repair process was impaired in functional Px group, but exogenous MEL replacement was able to restore this response. Thus, it is concluded that utilization of MEL may improve the bone repair in calvarial defects.

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“…Human bone mesenchymal stem cells (hBMSC) were immediately isolated and purified from bone marrow samples using density gradient centrifugation as previously described ( 22 ). Briefly, hBMSC were isolated from bone marrow blood collected during surgeries.…”

Section: Methodsmentioning

confidence: 99%

GnRHa/Stanozolol Combined Therapy Maintains Normal Bone Growth in Central Precocious Puberty

Zhu

Long

et al. 2021

Front. Endocrinol.

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BackgroundGonadotropin-releasing hormone agonist (GnRHa) is the gold standard in the treatment of Central Precocious Puberty (CPP) with progressive puberty and accelerative growth. However, GnRHa treatment is reported to result in growth deceleration and prevents growth plate development which leads to a reduction in height velocity. Stanozolol (ST) has been used to stimulate growth in patients with delayed growth and puberty, nevertheless, the effects and mechanisms of ST on CPP with GnRHa treatment are currently unclear.Methods and ResultsIn the current study, we recorded the following vital observations that provided insights into ST induced chondrogenic differentiation and the maintenance of normal growth plate development: (1) ST efficiently prevented growth deceleration and maintained normal growth plate development in rats undergoing GnRHa treatment; (2) ST suppressed the inhibitory effect of GnRHa to promote chondrogenic differentiation; (3) ST induced chondrogenic differentiation through the activation of the JNK/c-Jun/Sox9 signaling pathway; (4) ST promoted chondrogenic differentiation and growth plate development through the JNK/Sox9 signaling pathway in vivo.ConclusionsST mitigated the inhibitory effects of GnRHa and promoted growth plate development in rats. ST induced the differentiation of chondrocytes and maintained normal growth plate development through the activation of JNK/c-Jun/Sox9 signaling. These novel findings indicated that ST could be a potential agent for maintaining normal bone growth in cases of CPP undergoing GnRHa treatment.

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Wnt4 signaling mediates protective effects of melatonin on new bone formation in an inflammatory environment

Cited by 29 publications

References 48 publications

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

The influence of functional pinealectomy and exogenous melatonin application on healing of a burr hole in adult rat calvaria: a histological and immunohistochemical study

GnRHa/Stanozolol Combined Therapy Maintains Normal Bone Growth in Central Precocious Puberty

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