OPG inhibits insulin secretion from β-cells under inflammatory conditions.

<p>When β-cells are exposed to inflammatory stimuli, they secrete OPG, which blocks RANKL-RANK signaling. Both osteoblast- and β-cell-derived OPG negatively regulates insulin secretion. Lower panel was adopted from Wei and Karsenty (2015) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146544#pone.0146544.ref045" target="_blank">45</a>]. Glu, undercarboxylated. Gla, carboxylated.</p

Bone homeostasis in mice after <i>Salmonella</i> infection.

<p>(A) TRAP staining of tibial sections of BALB/c mice infected for 5 days with <i>Salmonella enterica</i>. Cont, uninfected mice; PsB, periosteal bone; TB, trabecular bone. Scale bars in upper panels represent 500 μm, and in middle or lower panels, 200 μm. (B, C) The number of osteoclasts (N.OC) at the trabecular bone surface (TBS) and the periosteal bone surface (PsBS) in tibial sections. Shown are means ± SD. Sal, <i>Salmonella</i>-infected mice. (D, E) Serum OPG levels (D) or RANKL levels (E) in mice infected one week with the avirulent <i>Salmonella enterica</i> strains UF20, UF71 and UF110 (n = 6 for each group). Open circles indicate outliers. ***<i>P</i> < 0.005. (F, G) Femoral bone tissue mineral density (TMD) in mice infected one week with avirulent <i>Salmonella</i>. Tb, trabecular; Ct, cortical. Shown are means ± SD. *<i>P</i> < 0.05 versus each control.</p

OPG expression in mouse β-cells and effect of OPG on glucose-stimulated insulin secretion.

<p>(A, B) Immunofluorescence analysis showing localization of OPG protein (red) with glucagon (green) (A) or insulin (green) (B) in pancreatic islets. OPG is predominantly expressed in β-cells based on co-localization with insulin. Scale bars, 20 μm. (C) Expression of <i>Opg</i>, <i>Rank</i>, and <i>Rankl</i> transcripts in isolated islets treated without or with LPS as measured by qPCR (n = 3–6). (D) Effect of LPS treatment on <i>Opg</i>, <i>Rank</i> and <i>Rankl</i> expression in MIN6 cells (n = 3). (E) Insulin secretion by MIN6 cells. Cells were untreated (n = 6) or treated with 100 ng/ml soluble RANKL (sRANKL, n = 6), 100 ng/ml recombinant OPG (rOPG, n = 6), 10 μg/ml LPS (n = 6), both LPS and sRANKL (n = 6), or both LPS and rOPG (n = 6), and then stimulated with 3, 9.8, or 20 mM glucose. Levels of secreted insulin were normalized to total cell protein. Shown are means ± SD. *<i>P</i> < 0.05, **<i>P</i> < 0.01.</p

Mice lacking OPG show altered glucose metabolism.

<p>(A) Fasting blood glucose levels (f.BGL) in control (<i>Opg</i>^+/±, n = 11, 8) and OPG knockout (<i>Opg</i>^-/-, n = 14, 9) mice 16 hr after injection of PBS or LPS. Shown are means ± SEM. ***<i>P</i> < 0.005. (B) Insulin signal intensity, calculated by insulin immunosignal intensity of cross-sections of pancreata of <i>Opg</i>^+/- and <i>Opg</i>^-/- mice 16 hr after injection of PBS or LPS (31Opg^+/± (n = 5, 4) and <i>Opg</i>^-/- (n = 8, 8) mice 16 hr after injection of PBS or LPS. Open circles indicate outliers. *<i>P</i> < 0.05. (D) Intraperitoneal glucose tolerance tests (IPGTT) of PBS- or LPS-injected <i>Opg</i>^+/- (n = 5, 4) or <i>Opg</i>^-/- (n = 6, 5) mice. Shown are means ± SEM. *<i>P</i> < 0.05. Blood glucose levels were measured at different time points, as indicated.</p

OPG production and biological marker analysis in liver and pancreas following LPS administration.

<p>(A, B) Serum OPG (A) or RANKL (B) levels in control PBS-injected or LPS-injected mice (n = 4 for each group). *<i>P</i> < 0.05, ***<i>P</i> < 0.005. (C) Fold-change in OPG protein levels in various organs isolated from LPS-injected relative to PBS-injected control mice (n = 3–5). Protein levels were normalized to total protein. Organs were collected 20 hr after injection of LPS (1 μg/g body weight) i.p. into 6- or 12-week-old C57BL/6J mice. Shown are means ± SEM. (D, E) Biochemical tests of liver and pancreatic function. Box plots show distribution of activities of aspartate transaminase (AST), alanine transaminase (ALT), and lipase (LIP) in serum samples collected from PBS-control or LPS-injected 10-week-old control (<i>Opg</i>^+/±) and OPG knockout (<i>Opg</i>^-/-) mice, 22 hr after injection. Open circles indicate outliers. ns, not significant. *<i>P</i> < 0.05, **<i>P</i> < 0.01.</p

Increased serum OPG levels in mice after microbial infection occurs via Fos family transcription factors.

<p>(A, B) Time-dependent elevation of OPG and IFN-β in serum, and colony forming units (CFU) in blood and spleen of 6-week-old C57BL/6J mice infected with <i>Salmonella enterica</i> χ3306 (A, n = 4 each point) or <i>Staphylococcus aureus</i> 92–1191 (B, n = 4 each point). “d” indicates death of one mouse. “ddd” indicates death of three mice. (C, D) Time-dependent elevation of OPG and IFN-β levels in serum after <i>Mycobacterium</i> (C, n = 4 each point) and influenza virus (D, n = 3 each point) infection of 6-week-old C57BL/6J mice. *<i>P</i> < 0.05, **<i>P</i> < 0.01, ***<i>P</i> < 0.005. (E, F) OPG serum levels in LPS-injected mice in c-Fos knockout mice (<i>Fos</i>^-/-) (E) or Fosl1 transgenic mice (<i>Fosl1</i>) (F) plus respective littermate controls (n = 3–4). Shown are means ± SD. *<i>P</i> < 0.05, **<i>P</i> < 0.01. LPS (4 μg/g body weight) was administered i.p. to 6-week-old C57BL/6J mice, and blood was collected 12 hr later.</p

Propuesta de una estrategia competitiva de administración y gestión del talento humano Grupo PROAMSA

Seminario de graduación (licenciatura en dirección de empresas)UCR::Vicerrectoría de Docencia::Ciencias Sociales::Facultad de Ciencias Económicas::Escuela de Administración de Negocio

Effects of W9 and risedronate administration on Wnt/β-catenin signaling of alveolar bone in <i>OPG</i>^<i>-/-</i> mice.

<p>(A) Histological analysis of the interradicular septum of the first molar (M1) in maxillae from WT and <i>OPG</i>^–/–mice treated with and without W9 or risedronate. β-catenin staining of WT and <i>OPG</i>^–/–mice. β-catenin-positive cells in nuclei (brown) were observed in the M1 interradicular septum in alveolar bone areas. (B) Sclerostin and TRAP double staining of WT and <i>OPG</i>^–/–mice. Sclerostin-positive osteocytes (brown) were observed in the M1 interradicular septum in alveolar bone areas. Sclerostin-positive osteocytes are indicated by black arrows. (C) The number of sclerostin-positive cells/bone area (N/mm²) was determined in the M1 interradicular septum (<i>n</i> = 5). Data are expressed as the mean ± SD. *: p<0.05. Scale bar, 50 μm.</p

Histomorphometric analysis of the protective effects of W9 on alveolar bone loss in <i>OPG</i>^<i>-/-</i> mice.

<p>Histomorphometric analysis of the protective effects of W9 on alveolar bone loss in <i>OPG</i>^<i>-/-</i> mice.</p