title: Osteoprotective Effects of Estrogen in the Maxillary Bone Depend on ERα.
abstract: Estrogen deficiency results in disruption of maxillary alveolar bone microarchitecture. Most of the actions of estrogen in long bones occur via estrogen receptor α (ERα). However, the function of ERα in the maxillary bone has not been defined. We aimed to investigate the role and underlying mechanisms of ERα in the physiological and mechanically induced alveolar bone remodeling in female and male mice. Wild-type (WT) and ERα(-/-) (ERKOα) mice were subjected to mechanically stimulated bone remodeling by inducing orthodontic tooth movement (OTM). The maxillary bone was analyzed using histomorphometric analysis, micro-computed tomography, quantitative polymerase chain reaction, and energy-dispersive spectroscopy. Bone marrow cells (BMCs) from WT and ERKOα mice were tested for their capacity to differentiate into osteoblasts and osteoclasts. Both male and female ERKOα mice exhibited marked reduction of alveolar bone mass and increased OTM. This response was associated with an increased number of osteoclasts and reduced number of apoptotic cells and osteoblasts in the periodontium and alveolar bone. Consistently, ERKOα mice exhibited lower levels of calcium in bone and increased expression of IL-33 (interleukin-33), TNF-α (tumor necrosis factor α), and IL-1β (interleukin-1β) and decreased expression of dentin matrix acidic phosphoprotein and alkaline phosphatase in periodontal tissues. Moreover, the differentiation of osteoclasts and osteoblasts in vitro was significantly higher in BMCs obtained from ERKOα. ERα is required to maintain the microarchitecture of maxillary alveolar bone. This process is linked to bone cell differentiation and apoptosis, as well as local production of inflammatory molecules such as IL-33, TNF-α, and IL-1β.
authors.affiliation: Department of Oral Pathology and Surgery, Faculty of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Macari
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand.
authors.forename: L
authors.initials: L
authors.lastname: Ajay Sharma
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand.
authors.forename: A
authors.initials: A
authors.lastname: Wyatt
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand.
authors.forename: P
authors.initials: P
authors.lastname: Knowles
authors.affiliation: Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: R E
authors.initials: RE
authors.lastname: Szawka
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, São Paulo University, Bauru, SP, Brazil.
authors.forename: G P
authors.initials: GP
authors.lastname: Garlet
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand.
authors.forename: D R
authors.initials: DR
authors.lastname: Grattan
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand.
authors.forename: G J
authors.initials: GJ
authors.lastname: Dias
authors.affiliation: Department of Oral Pathology and Surgery, Faculty of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil tarcilia@ufmg.br.
authors.forename: T A
authors.initials: TA
authors.lastname: Silva
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000502:physiology; D016723:Bone Remodeling; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D047628:Estrogen Receptor alpha / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism; D008297:Male; D008437:Maxilla / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010052:Ovariectomy; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D013052:Spectrometry, X-Ray Emission; D014087:Tooth Movement Techniques; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: C513308:Dmp1 protein, mouse; D047628:Estrogen Receptor alpha; D016326:Extracellular Matrix Proteins; D053583:Interleukin-1beta; D000067596:Interleukin-33; D014409:Tumor Necrosis Factor-alpha; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: alveolar bone loss; bone remodeling; estrogen receptor alpha; interleukin-33; maxilla; osteoporosis