Histological evidence that metformin reverses the adverse effects of diabetes on orthodontic tooth movement in rats

Sun, Jing; Du, Juan; Feng, Wei; Lu, Boyao; Liu, Hongrui; Guo, Jie; Amizuka, Norio; Li, Minqi

doi:10.1007/s10735-016-9707-y

Cited by 27 publications

(34 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies utilizing various in vivo models of insulin resistance and/or hyperglycemia also generally confirm that metformin monotherapy is bone‐friendly, with ability to counteract the detrimental effects of diabetes on bone. Specifically, metformin has been shown to prevent or correct the diabetes‐induced alterations in bone microarchitecture and/or bone histology in models of partial insulin deficiency and in models of insulin resistance, diet‐induced obesity, or metabolic syndrome . At the same time, bone marrow adipose expansion, characteristic of mice fed a high‐fat diet, was also correctible with metformin .…”

Section: Drugs and Bonementioning

confidence: 99%

Diabetes pharmacotherapy and effects on the musculoskeletal system

Kalaitzoglou

Fowlkes

Popescu

et al. 2018

Diabetes Metabolism Res

View full text Add to dashboard Cite

Summary Persons with type 1 or type 2 diabetes have a significantly higher fracture risk than age‐matched persons without diabetes, attributed to disease‐specific deficits in the microarchitecture and material properties of bone tissue. Therefore, independent effects of diabetes drugs on skeletal integrity are vitally important. Studies of incretin‐based therapies have shown divergent effects of different agents on fracture risk, including detrimental, beneficial, and neutral effects. The sulfonylurea class of drugs, owing to its hypoglycemic potential, is thought to amplify the risk of fall‐related fractures, particularly in the elderly. Other agents such as the biguanides may, in fact, be osteo‐anabolic. In contrast, despite similarly expected anabolic properties of insulin, data suggests that insulin pharmacotherapy itself, particularly in type 2 diabetes, may be a risk factor for fracture, negatively associated with determinants of bone quality and bone strength. Finally, sodium‐dependent glucose co‐transporter 2 inhibitors have been associated with an increased risk of atypical fractures in select populations, and possibly with an increase in lower extremity amputation with specific SGLT2I drugs. The role of skeletal muscle, as a potential mediator and determinant of bone quality, is also a relevant area of exploration. Currently, data regarding the impact of glucose lowering medications on diabetes‐related muscle atrophy is more limited, although preclinical studies suggest that various hypoglycemic agents may have either aggravating (sulfonylureas, glinides) or repairing (thiazolidinediones, biguanides, incretins) effects on skeletal muscle atrophy, thereby influencing bone quality. Hence, the therapeutic efficacy of each hypoglycemic agent must also be evaluated in light of its impact, alone or in combination, on musculoskeletal health, when determining an individualized treatment approach. Moreover, the effect of newer medications (potentially seeking expanded clinical indication into the pediatric age range) on the growing skeleton is largely unknown. Herein, we review the available literature regarding effects of diabetes pharmacotherapy, by drug class and/or by clinical indication, on the musculoskeletal health of persons with diabetes.

show abstract

Section: Drugs and Bonementioning

confidence: 99%

Diabetes pharmacotherapy and effects on the musculoskeletal system

Kalaitzoglou

Fowlkes

Popescu

et al. 2018

Diabetes Metabolism Res

View full text Add to dashboard Cite

show abstract

“…Orthodontic tooth movement (OTM) occurs through controlled application of mechanical forces to the tooth, which leads to required changes in the periodontal ligament and alveolar bone and subsequently activates remodeling of the alveolar bone (Verna et al 1999 ; Nakamura et al 2008 ; Tsuge et al 2016 ; Sun et al 2017 ). The periodontal ligament, a connective mechanosensitive fibrous soft tissue located between the root and the alveolar bone, mediates the loading force from tooth to alveolar bone, and thus creates the necessary conditions for cells to participate in alveolar bone remodeling (Liu et al 2013 ; Mabuchi et al 2002 ; Cui et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Tension force-induced bone formation in orthodontic tooth movement via modulation of the GSK-3β/β-catenin signaling pathway

et al. 2017

View full text Add to dashboard Cite

Orthodontic force-induced osteogenic differentiation and bone formation at tension sites play a critical role in orthodontic tooth movement. However, the molecular mechanism underlying this phenomenon is poorly understood. In the current study, we investigated the involvement of the GSK-3β/β-catenin signaling pathway, which is critical for bone formation during tooth movement. We established a rat tooth movement model to test the hypothesis that orthodontic force may stimulate bone formation at the tension site of the moved tooth and promote the rate of tooth movement via regulation of the GSK-3β/β-catenin signaling pathway. Our results showed that continued mechanical loading increased the distance between the first and second molar in rats. In addition, the loading force increased bone formation at the tension site, and also increased phospho-Ser9-GSK-3β expression and β-catenin signaling pathway activity. Downregulation of GSK-3β activity further increased bone parameters, including bone mineral density, bone volume to tissue volume and trabecular thickness, as well as ALP- and osterix-positive cells at tension sites during tooth movement. However, ICG-001, the β-catenin selective inhibitor, reversed the positive effects of GSK-3β inhibition. In addition, pharmaceutical inhibition of GSK-3β or local treatment with β-catenin inhibitor did not influence the rate of tooth movement. Based on these results, we concluded that GSK-3β/β-catenin signaling contributes to the bone remodeling induced by orthodontic forces, and can be used as a potential therapeutic target in clinical dentistry.

show abstract

“…According to the results of numerous clinical observations and experimental studies, pathological changes in bone tissue, significant microcirculatory disorders, and neurotrophic disorders were identified among the preexis ting adverse factors affecting the course of the postoperative period of patients with DM. At the same time, it is believed that osteopenia and osteoporosis, as the most frequent pathological changes in bone tissue, have the diffuse character, since both cancellous and tubular bones "suffer" [14]. Conducted histomorphometric studies have shown that in case of diabetes mellitus type 1 there is a reduced bone formation with a decrease in metabolic processes in it.…”

Section: Discussionmentioning

confidence: 99%

Specific aspects of the radiographic morphometric and densitometric characteristics of mandible of the rats with experimental diabetes mellitus after tooth extraction

2019

View full text Add to dashboard Cite

Diabetes mellitus is regarded today as a metabolic disease, which is considered to be a modulator of endodontic infections, is responsible for altering the immune and inflammatory responses, impedes the healing process, and contributes to damage of organs and tissues of the body, including tooth pulp and periapical tissues.The aim of the work is to study the radiographic characteristics of the dental septum of the alveolar crest of the mandible, crown and root of the low molars of rats with experimental streptozotocin diabetes at different times of the post-extraction period (the 1 st , 7 th and 14 th day). Materials and methods.Studies were conducted on 120 male Wistar rats, 8-10 months old, divided into eight groups of 15 animals each. The experimental diabetes mellitus was modelled in 45 animals by a single administration of streptozotocin interperitoneally (SIGMA Chemical, the USA) at a dose of 50 mg/kg, diluted in 0.5 ml of 0.1 M citrate buffer (pH 4.5) ex tempore, on the 21 st day after its induction the level of fasting glucose was determined (by the glucose oxidise method using standard test strips Test Strip II, glucometer Glucocard, Japan), which was 24.7 ± 2.2 mM/l. The extraction of the first low molar of the right mandible was realised using thiopental anaesthesia (40 mg / kg dose) with additional local infiltration anaesthesia with Ubistesine (3M Deutschland GmbH, Germany).On the 1 st , 7 th , and 14 th day, dates that correspond to the experiment after the extraction of the tooth, the rats were decapitated using thiopental anaesthesia (dose 40 mg/kg).The visiography of the mandible was performed using a computerized 3D CBCT tomograph Panoura 18S Panoramic 3D. With the help of digital image analysis the radiographic density of tissues of the alveolar socket of the removed 1 st molar, crown of the 1 st , 2 nd and 3 rd molars, their root and dental septum of the alveolar crest were determined.The results. Radiological density of the interalveolar and interradicular septa between the 1 st -3 rd molar and the 1 st molar root, which is the most traumatized and loaded rats' tooth, is decreased in the rats with experimental diabetes mellitus. Tooth extraction in the rats with diabetes mellitus results in the increase (not in the decrease as it is observed in control group) of radiological density a day after in the alveolar socket and the adjacent 2 nd and 3 rd molars, that may be caused by significant infiltration related to the secondary alteration. The final stage of the local inflammatory reaction resorptive phase that corresponds to the 7 th day of post-extraction period is characterized by almost complete restoration of the alveolar socket radiological density in the control rats, whereas in the rats with diabetes mellitus radiological density of the studied sites decreases and this process continues on the 14 th day. Conclusions.In the work it was found out that the extraction of a tooth in rats with normal carbohydrate metabolism is accompanied by dynamic changes in radiological density not only in...

show abstract

Histological evidence that metformin reverses the adverse effects of diabetes on orthodontic tooth movement in rats

Cited by 27 publications

References 46 publications

Diabetes pharmacotherapy and effects on the musculoskeletal system

Diabetes pharmacotherapy and effects on the musculoskeletal system

Tension force-induced bone formation in orthodontic tooth movement via modulation of the GSK-3β/β-catenin signaling pathway

Specific aspects of the radiographic morphometric and densitometric characteristics of mandible of the rats with experimental diabetes mellitus after tooth extraction

Contact Info

Product

Resources

About