Effects of metformin on the osteogenesis of alveolar BMSCs from diabetic patients and implant osseointegration in rats

Sun, Rongxin; Liang, Chao; Sun, Yujie; Xu, Yifan; Geng, Wei; Li, Jun

doi:10.1111/odi.13808

Cited by 27 publications

(34 citation statements)

References 37 publications

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“…Based on our results, it is likely that both changes in the bone structure and composition likely contribute to the increased fixation strength reported in preclinical animal models 24 . Commonly prescribed T2DM medications, including metformin 43 and insulin, 44 have also been reported to increase osseointegration in diabetic rats. However, whether these same treatments increase implant fixation strength or bone matrix composition is currently unknown.…”

Section: Discussionmentioning

confidence: 53%

The relative contribution of bone microarchitecture and matrix composition to implant fixation strength in rats

Anderson

Fullam

et al. 2021

Journal Orthopaedic Research

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Bone microarchitectural parameters significantly contribute to implant fixation strength but the role of bone matrix composition is not well understood. To determine the relative contribution of microarchitecture and bone matrix composition to implant fixation strength, we placed titanium implants in 12‐week‐old intact Sprague–Dawley rats, ovariectomized‐Sprague–Dawley rats, and Zucker diabetic fatty rats. We assessed bone microarchitecture by microcomputed tomography, bone matrix composition by Raman spectroscopy, and implant fixation strength at 2, 6, and 10 weeks postimplantation. A stepwise linear regression model accounted for 83.3% of the variance in implant fixation strength with osteointegration volume/total volume (50.4%), peri‐implant trabecular bone volume fraction (14.2%), cortical thickness (9.3%), peri‐implant trabecular crystallinity (6.7%), and cortical area (2.8%) as the independent variables. Group comparisons indicated that osseointegration volume/total volume was significantly reduced in the ovariectomy group at Week 2 (~28%) and Week 10 (~21%) as well as in the diabetic group at Week 10 (~34%) as compared with the age matched Sprague–Dawley group. The crystallinity of the trabecular bone was significantly elevated in the ovariectomy group at Week 2 (~4%) but decreased in the diabetic group at Week 10 (~3%) with respect to the Sprague–Dawley group. Our study is the first to show that bone microarchitecture explains most of the variance in implant fixation strength, but that matrix composition is also a contributing factor. Therefore, treatment strategies aimed at improving bone‐implant contact and peri‐implant bone volume without compromising matrix quality should be prioritized.

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Section: Discussionmentioning

confidence: 53%

The relative contribution of bone microarchitecture and matrix composition to implant fixation strength in rats

Anderson

Fullam

et al. 2021

Journal Orthopaedic Research

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“…For example, Metformin promoted osteogenic differentiation of hBMSCs through inhibiting phosphorylation of GSK3β via activating AMPK and Wnt signaling pathway [ 48 ]. In another study, the implant osseointegration in a rat model was promoted by Metformin dependently through AMPK/BMP/Smad signalling pathway [ 49 ]. As an adipocyte-specific factor, APN has been found to promote osteogenic differentiation of stem cells.…”

Section: Discussionmentioning

confidence: 99%

The lncRNA H19/miR-541-3p/Wnt/β-catenin axis plays a vital role in melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells

Han

Tian

Huang

et al. 2021

Aging

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Implant dentures become the first choice for denture restoration in patients with tooth loss. However, oral implants often fail in osteoporosis (OP) patients. Melatonin (MT) induces osteogenic differentiation of bone mesenchymal stem cells (BMSCs), suggesting its therapeutic potential in OP treatment. Long non-coding RNA H19 induces osteogenic differentiation of BMSCs, while its regulatory mechanism in MT-involved osteogenic and adipogenic differentiation of BMSCs remains elusive. Ovariectomized (OVX) rat was used to construct an OP model, and bone quality was assessed. Meanwhile, the expression of H19, miR-541-3p, MT and adiponectin (APN) was examined by quantitative reverse transcription-PCR (qRT-PCR) or ELISA. The adipogenic and osteogenic differentiation of BMSCs were determined by oil red O staining and alizarin red S staining, respectively. The targeting relationships between H19, miR-541-3p and APN mRNA were predicted by bioinformatics and confirmed by RNA immunoprecipitation and dual-luciferase reporter assay. The results showed that MT, H19 and APN were down-regulated, while miR-541-3p was up-regulated in the OVX rat model. At the cellular level, MT reduced adipogenic differentiation, heightened osteogenic differentiation of BMSCs, and activated Wnt/β-catenin pathway, which were reversed by the MT2 selective inhibitor 4-P-PDOT. Overexpressing H19 facilitated the osteogenic differentiation and inhibited the adipogenic differentiation of BMSCs mediated by MT, while H19 knockdown or overexpressing miR-541-3p had the opposite effect. Moreover, H19 functioned as a competitive endogenous RNA and sponged miR-541-3p, and miR-541-3p targeted APN. Overall, MT modulates the osteogenic and adipogenic differentiation of BMSCs by mediating H19/miR-541-3p/APN axis, providing a new reference for the targeted therapy of OP.

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“…It has been established that insulin can reverse osteoblast disorders, and the combined use of other agents can accelerate this process. Resveratrol, metformin, and other related drugs have also been found to promote the osteogenesis and osseointegration of diabetic alveolar bone mesenchymal stem cells ( Hua et al, 2020 ; Sun et al, 2021 ). Moreover, material modifications such as micro- and nano-topographically complex implant surfaces can promote early bone anchorage in diabetic patients ( Ajami et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Hormone and implant osseointegration: Elaboration of the relationship among function, preclinical, and clinical practice

Yin²,

Sun³

et al. 2022

Front. Mol. Biosci.

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As clusters of peptides or steroids capable of high-efficiency information transmission, hormones have been substantiated to coordinate metabolism, growth, development, and other physiological processes, especially in bone physiology and repair metabolism. In recent years, the application of hormones for implant osseointegration has become a research hotspot. Herein, we provide a comprehensive overview of the relevant reports on endogenous hormones and their corresponding supplementary preparations to explore the association between hormones and the prognosis of implants. We also discuss the effects and mechanisms of insulin, parathyroid hormone, melatonin, vitamin D, and growth hormone on osseointegration at the molecular and body levels to provide a foothold and guide future research on the systemic conditions that affect the implantation process and expand the relative contraindications of the implant, and the pre-and post-operative precautions. This review shows that systemic hormones can regulate the osseointegration of oral implants through endogenous or exogenous drug-delivery methods.

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Effects of metformin on the osteogenesis of alveolar BMSCs from diabetic patients and implant osseointegration in rats

Cited by 27 publications

References 37 publications

The relative contribution of bone microarchitecture and matrix composition to implant fixation strength in rats

The relative contribution of bone microarchitecture and matrix composition to implant fixation strength in rats

The lncRNA H19/miR-541-3p/Wnt/β-catenin axis plays a vital role in melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells

Hormone and implant osseointegration: Elaboration of the relationship among function, preclinical, and clinical practice

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