Adiponectin regulates BMSC osteogenic differentiation and osteogenesis through the Wnt/β-catenin pathway

Wang, Yiyao; Zhang, Xiaohui; Shao, Jun; Liu, Hanghang; Liu, Xian; Luo, En

doi:10.1038/s41598-017-03899-z

Cited by 96 publications

(81 citation statements)

References 63 publications

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“…Besides, the protective effect has been found even at nonweight-bearing bone sites [32]. Thus, another explanation has been proposed that some adipokines such as adiponectin [33], resistin [34], secreted by adipose tissue stimulate bone formation by inducing the differentiation of mesenchymal stem cells (MSCs) to osteoblast and increasing osteoblast proliferation. The positive associations of obesity with BMD in our study support these mechanisms and provide support for the obesity effects on osteoporosis.…”

Section: Biological Mechanism Of Obesity and Osteoporosismentioning

confidence: 99%

Adiposity reduces the risk of osteoporosis in Chinese rural population: the Henan rural cohort study

et al. 2020

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Background: Adiposity plays a crucial role in the risk of osteoporosis. However, the impact of body fat distribution on the skeleton is contentious. The study was designed to explore the association of various adiposity indices with estimated bone mineral density (BMD) and the risk of osteoporosis based on body mass index (BMI), body fat percentage (BFP), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), and visceral fat index (VFI). Methods: A total of 8475 subjects derived from the Henan Rural Cohort Study were analyzed. The estimated BMD of study participants were measured by calcaneal quantitative ultrasound (QUS). Linear regression and binary logistic regression were performed to estimate the association of adiposity and the outcomes. Results: The mean age of the study participants was 55.23 ± 11.09 years and 59.61% were women. The crude and age-standardized prevalence of high osteoporosis risk was 16.24 and 11.82%. Per unit increment in adiposity indices was associated with 0.005-0.021 g/cm 2 increase in estimated BMD. The adjusted odds ratios (95% confidence interval) for high osteoporosis risk in per 1 SD increase of WC, WHR, WHtR, BMI, BFP, and VFI were 0.820 (0.748, 0.898), 0.872 (0.811, 0.938), 0.825 (0.765, 0.891), 0.798 (0.726, 0.878), 0.882 (0.800, 0.972), and 0.807 (0.732, 0.889), respectively. Stratified analyses indicated greater effects on individuals aged 55 years or older. Conclusions: The adiposity indices have an inverse association with the risk of osteoporosis among Chinese rural population, especially in the elderly.

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Section: Biological Mechanism Of Obesity and Osteoporosismentioning

confidence: 99%

Adiposity reduces the risk of osteoporosis in Chinese rural population: the Henan rural cohort study

et al. 2020

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“…The importance of both canonical and noncanonical Wnt signalling in the osteogenesis of stem cells has been widely explored in many studies in vivo and in vitro [12,13]. Wnt5a signalling suppresses adipogenesis by suppressing the transcriptional activity of PPAR-γ and promotes the differentiation of BMSCs into osteoblasts [14,15].…”

Section: Introductionmentioning

confidence: 99%

Wnt5a/FZD4 Mediates the Mechanical Stretch-Induced Osteogenic Differentiation of Bone Mesenchymal Stem Cells

Tian

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Mechanical stimulation and WNT signalling have essential roles in regulating the osteogenic differentiation of bone marrow stromal cells (BMSCs) and bone formation. However, little is known regarding the regulation of WNT signalling molecule expression and therefore the osteogenic differentiation of BMSCs during osteogenesis. Methods: Microarrays of BMSCs from elderly individuals or patients with osteoporosis (GSE35959) from the GEO database were analysed using GeneSight-Lite 4.1.6 (BioDiscovery) and C2 curated gene sets downloaded from Molecular Signatures Database (MSigDB). Realtime PCR and western blotting were used to measure the expression of the indicated genes. ALP and Alizarin red staining were used to evaluate the osteogenesis of BMSCs. Results: In this study, we investigated whether mechanical loading directly regulates the expression of WNT signalling molecules and examined the role of WNT signalling in mechanical loading-triggered osteogenic differentiation and bone formation. We first studied the microarrays of samples from patients with osteoporosis and found downregulation of the GPCR ligand binding gene set in the BMSCs of patients with osteoporosis. Then, we demonstrated that mechanical stimuli can regulate osteogenesis and bone formation both in vivo and in vitro. FZD4 was upregulated during cyclic mechanical stretch (CMS)-induced osteogenic differentiation, and the JNK signalling pathway was activated. FZD4 knockdown inhibited the mechanical stimuli-induced osteogenesis and JNK activity. More importantly, we found an activating effect of WNT5A and FZD4 that regulated bone formation in response to hindlimb unloading in mice, and pretreatment with WNT5A or activation of the expression of FZD4 partly rescued the osteoporosis caused by mechanical unloading. Conclusions: Our results demonstrate, for the first time, that mechanical stimulation alters the expression of genes involved in the osteogenic differentiation of BMSCs via the direct regulation of FZD4 and that therapeutic WNT5A and FZD saRNA may be an efficient strategy for enhancing bone formation under mechanical stimulation.

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“…Wnt/β-catenin pathway is a classic signal exerts multiple roles in cellular behaviors (40,41). APC, which act as a negative regulator in Wnt/β-catenin, notably binds to β-catenin and inhibits its' unclear transferring (42).…”

Section: Discussionmentioning

confidence: 99%

Human amnion-derived mesenchymal stem cells promote osteogenic differentiation of lipopolysaccharide-induced human bone marrow mesenchymal stem cells via ANRIL/miR-125a/APC axis

Wang

Lv²,

Huang

et al. 2020

Preprint

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Background: Periodontitis is a chronic inﬂammatory disease inducing the absorption of alveolar bone and leading to tooth loss. Human amnion-derived mesenchymal stem cells (HAMSCs) have been studied as a potential strategy for inﬂammatory processes. Here, we explored the role of long non-coding RNA (LncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) in HAMSCs-droved osteogenesis in lipopolysaccharide (LPS)-induced human bone marrow mesenchymal stem cells (HBMSCs). Methods: Cells were incubated with coculture system. Reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity were used to detect oxidative stress level. Flow cytometry was performed to determine the cell proliferation. The Alkaline phosphatase (ALP) and Alizarin red assay, cell transfection and rat mandibular defect model were used to evaluate the osteogenic differentiation. Quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), Western blot, dual-luciferase reporter assay and immunofluorescence Staining were used to evaluate the molecular mechanisms.Results: Here, we discovered that HAMSCs promoted osteogenesis of LPS-induced HBMSCs, while ANRIL level in HBMSCs was decreased during coculturing. ANRIL had no significant influence on the proliferation of LPS-induced HBMSCs, while its overexpression inhibited the HAMSCs-droved osteogenesis in vivo and in vitro; whereas its knockdown reversed these effects. Mechanistically, we found that downregulating ANRIL led to overexpression of microRNA-125a (miR-125a), and further contributed to the competitively bounding of miR-125a and Adenomatous polyposis coli (APC), thus significantly activating the Wnt/β-catenin pathway. Conclusions: Our study indicates that HAMSCs promote osteogenic differentiation of LPS-induced HBMSCs via ANRIL/miR-125a/APC axis, and offer a novel approach for periodontitis therapy.

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Adiponectin regulates BMSC osteogenic differentiation and osteogenesis through the Wnt/β-catenin pathway

Cited by 96 publications

References 63 publications

Adiposity reduces the risk of osteoporosis in Chinese rural population: the Henan rural cohort study

Adiposity reduces the risk of osteoporosis in Chinese rural population: the Henan rural cohort study

Wnt5a/FZD4 Mediates the Mechanical Stretch-Induced Osteogenic Differentiation of Bone Mesenchymal Stem Cells

Human amnion-derived mesenchymal stem cells promote osteogenic differentiation of lipopolysaccharide-induced human bone marrow mesenchymal stem cells via ANRIL/miR-125a/APC axis

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