Oestrogen receptor β (ERβ) regulates osteogenic differentiation of human dental pulp cells

Abstract

Estradiol (E) has many important actions in the tissues of the oral cavity. Disruption of E metabolism or alterations in systemic E concentrations have been associated with compromised periodontal health. In many instances such changes occur secondarily to the well characterised effects of E on bone physiology -especially maintenance of bone mineral density (BMD). Despite these important epidemiological findings, little is known about the mechanism of action of E in oral tissues or the expression and function of oestrogen receptor (ER) isoforms in these tissues. We have isolated human dental pulp cells (hDPCs), which are able to differentiate towards an osteogenic lineage under appropriate culture conditions. We show that hDPCs express ERα, ERβ1, ERβ2 and the cell membrane associated G protein-coupled ER (GPR30). Following osteogenic differentiation of hDPCs, ERβ1 and ERβ2 were up regulated approximately 50-fold while ERα and GPR30 were down regulated, but to a much lesser degree (approximately 2-fold). ERβ was characterised as a 59kDa protein following Western blot analysis with validated antibodies and ERβ was detected in both nuclear and cytoplasmic cell compartments following immunofluorescence (IF) and immunohistochemical (IHC) analysis of cultured cells. Furthermore isoform specific antibodies detected both ERβ1 and ERβ2 in DPC cultures and in situ analysis of ERβ expression in decalcified tooth/pulp sections identified the odontoblast layer of pulp cells juxtaposed to the tooth enamel as strongly reactive for both ERβ isoforms. Finally the use of isoform specific agonists identified ERβ as the main receptor responsible for the pro-osteogenic effect of oestrogenic hormones in this tissue. Our data suggest that oestrogens stimulated osteogenic differentiation in hDPCs and that this action is mediated principally through the ERβ isoform. These findings may have important consequences for the investigation and treatment of oral and periodontal pathologies which are associated with imbalances in oestrogen concentrations and action.

Dimorphism in Dental Tissues: Sex differences in Archaeological Individuals for Multiple Tooth Types

“…Changes in dentine thickness before and after puberty have been shown to coincide with changing levels of testosterone (Zilberman and Smith, 2001). Growth hormone receptors have also been discovered in dental tissues acting as regulators of growth (Young et al, 1992; Zhang et al, 1997, 2005; Litsas, 2015); they are influenced by oestrogens and others sex hormones (Hietala et al, 1998; Meinhardt and Ho, 2006; Inaba et al, 2013; Houari et al, 2016; Alhodhodi et al, 2017). Research suggests that oestrogen and androgen receptors within the dental pulp play a role in dentinogenesis (Inaba et al, 2013).…”

The History of the Study of Endometriosis and the Impact of Humoral and Immune Factors on Its Pathogenesis

“…При сравнении эктопического и эутопического эндометрия было обнаружено, что концентрация мРНК, кодирующих SLIT3, в первом значительно превышала таковой во втором. Эстрогензависимую регуляцию экспрессии SLIT3 исследовали с помощью 17β-эстродиола и селективных агонистов для каждого подтипа рецептора эстрогена (для ERα-4-[2,3-би (4-гидроксифенил) -4-пропил-1Н-пиразол-5-илиден] циклогексо-2,5-диен-1-он (PPT) [7] ; для ERβ-2,3-би (4-гидроксифенил) пропионитрил (DPN) [8] ). С помощью функциональных анализов подтвердили, что SLIT3 в большей степени влияет на ангиогенез.…”

Co-expression of the aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) in the developing teeth of rat offspring after rat mothers’ exposure to 2,3,7,8-tetrachlorodib

“…23,24 Estrogens play an important role during tooth development and its survivability in the surrounding tissues. 25,26 Alhodhodi et al suggest that estrogens stimulate osteogenic differentiation and that this action is mediated mainly through the ERβ isoform. These findings may have profound consequences in terms of the investigation and treatment of oral pathologies, which are associated with imbalances in estrogen concentrations.…”

“…These findings may have profound consequences in terms of the investigation and treatment of oral pathologies, which are associated with imbalances in estrogen concentrations. 24,26 Nebel proved that estrogen affects chemokine expression in periodontal cells, which shows a complex pattern involving downregulation as well as upregulation of chemokines. Estrogen exerts both anti-inflammatory and proinflammatory effects through these mechanisms.…”