title: Histological evidence that metformin reverses the adverse effects of diabetes on orthodontic tooth movement in rats.
abstract: This study evaluated the effects of metformin on orthodontic tooth movement in a rat model of type 2 diabetes mellitus. Rats were fed a high-fat diet for 4 weeks to induce fat accumulation and insulin resistance, and then injected with a low dose of streptozotocin (35 mg/kg) intraperitoneally to induce type 2 diabetes. An orthodontic appliance was placed in normoglycemic, type 2 diabetes, and type 2 diabetes with metformin-administrated rats. After 14 days, type 2 diabetes rats exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphatase-positive osteoclasts, stronger cathepsin K expression, and weaker alkaline phosphatase immunostaining than normoglycemic rats. Metformin administration resulted in normalization of osteoclast numbers, cathepsin K immunostaining, and of tooth movement as well as partly recovery of alkaline phosphatase expression in diabetic rats. Metformin also reduced sclerostin expression and improved the immunolocalization of dentin matrix protein 1 in osteocytes of type 2 diabetes rats. These results suggest that metformin administration reversed the adverse effects of diabetes on orthodontic tooth movement.
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Bone Metabolism, School of Stomatology, Shandong University, Wenhua West Road 44-1, Jinan, 250012, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Bone Metabolism, School of Stomatology, Shandong University, Wenhua West Road 44-1, Jinan, 250012, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Bone Metabolism, School of Stomatology, Shandong University, Wenhua West Road 44-1, Jinan, 250012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Boyao
authors.initials: B
authors.lastname: Lu
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Bone Metabolism, School of Stomatology, Shandong University, Wenhua West Road 44-1, Jinan, 250012, China.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Bone Metabolism, School of Stomatology, Shandong University, Wenhua West Road 44-1, Jinan, 250012, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
authors.affiliation: Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Bone Metabolism, School of Stomatology, Shandong University, Wenhua West Road 44-1, Jinan, 250012, China. liminqi@sdu.edu.cn.
authors.forename: Minqi
authors.initials: M
authors.lastname: Li
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D056657:Cathepsin K; D048909:Diabetes Complications / Q000188:drug therapy; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D016326:Extracellular Matrix Proteins / Q000032:analysis; D007004:Hypoglycemic Agents; D008687:Metformin; D010010:Osteoclasts / Q000473:pathology; D010011:Osteocytes / Q000737:chemistry; D010750:Phosphoproteins / Q000032:analysis; D051381:Rats; D014086:Tooth Mobility / Q000188:drug therapy* / Q000209:etiology
chemical_list: C081635:Dmp1 protein, rat; D016326:Extracellular Matrix Proteins; D007004:Hypoglycemic Agents; D010750:Phosphoproteins; D008687:Metformin; D000469:Alkaline Phosphatase; D056657:Cathepsin K
keywords: Dentin matrix protein 1; Diabetes; Metformin; Orthodontic tooth movement; Sclerostin