Sex-Specific Effects of THRβ Signaling on Metabolic Responses to High Fat Diet in Mice.

Thyroid hormone (TH) plays a crucial role in regulating the functions of both bone and adipose tissue. Given that TH exerts its cholesterol-lowering effects in hepatic tissue through the TH receptor-β (TRβ), we hypothesized that TRβ agonist therapy using MGL3196 (MGL) would be effective in treating increased adiposity and bone loss in response to a 12-week high-fat diet (HFD) in adult C57BL/6J mice. Transcriptional and serum profiling revealed that HFD-induced leptin promoted weight gain in both males and females, but MGL only suppressed leptin induction and weight gain in males.

Global and Conditional Disruption of the Gene in Osteoblasts and/or Chondrocytes Unveils Epiphyseal and Metaphyseal Bone-Specific Effects of IGF-I in Bone.

To evaluate the relative importance of IGF-I expression in various cell types for endochondral ossification, we quantified the trabecular bone at the secondary spongiosa and epiphysis of the distal femur in 8-12-week-old male mice with a global knockout of the gene, as well as the conditional deletion of in osteoblasts, chondrocytes, and osteoblasts/chondrocytes and their corresponding wild-type control littermates. The osteoblast-, chondrocyte-, and osteoblast/chondrocyte-specific conditional knockout mice were generated by crossing floxed mice with Cre transgenic mice in which Cre expression is under the control of either the or promoter. We found that the global disruption of resulted in 80% and 70% reductions in bone size, defined as total volume, at the secondary spongiosa and epiphysis of the distal femur, respectively.

Vitamin D Deficiency (VDD) and Benefits of Supplementation in Veterans with IBS-D.

Many veterans deployed to Gulf War areas suffer from persistent chronic diarrhea that is disabling and affects their quality of life. The causes for this condition have eluded investigators until recently and recent literature has shed light on the effect of vitamin D on the brain-gut axis. This study focused on determining clinical causes contributing to diarrhea and assessed whether reversing the identified causes, specifically vitamin D deficiency (VDD), could reduce the incidence of diarrhea in Gulf War veterans (GWVs).

WNT16 Regulation of the Articular Chondrocyte Phenotype in Mice.

The anabolic effects of WNT16 on osteoblasts are well established, however, little is known regarding the role of WNT16 in chondrocytes. In this study, we evaluated expression and its biological effects on mouse articular chondrocytes (ACs), since these cells are key to the development of osteoarthritis. While ACs derived from the long bone epiphysis of 7-day old C57BL/6J mice express multiple s, represent the two most highly expressed s (expressed at several-fold higher levels than other s).

Development of an Animal Model for Traumatic Brain Injury Augmentation of Heterotopic Ossification in Response to Local Injury.

Heterotopic ossification (HO) is the abnormal growth of bone in soft connective tissues that occurs as a frequent complication in individuals with traumatic brain injury (TBI) and in rare genetic disorders. Therefore, understanding the mechanisms behind ectopic bone formation in response to TBI is likely to have a significant impact on identification of novel therapeutic targets for HO treatment. In this study, we induced repetitive mild TBI (mTBI) using a weight drop model in mice and then stimulated HO formation via a local injury to the Achilles tendon or fibula.

Strategic Management of Bleeding Small Bowel Gastrointestinal Angiodysplasias (GIADs): A 12 Year Retrospective Review in a Veteran Population and Cost Comparison.

Gastrointestinal angiodysplasias (GIADs), also known as gastrointestinal angioectasias, are dilated, abnormally thin-walled blood vessels that occur in the mucosa and submucosa throughout the gastrointestinal tract. As a common cause of small bowel bleeding, GIADs have a significant impact on patient's morbidity and healthcare costs. Presently, somatostatin has been used widely to treat GIADs, but it is unclear if other therapies are as beneficial and cost-effective as somatostatin in managing GIADs.

Contrasting effects of , an obesity gene, on trabecular bone volume and bone marrow adiposity.

Pathological obesity and its complications are associated with an increased propensity for bone fractures. Humans with certain genetic polymorphisms at the kinase suppressor of ras2 (KSR2) locus develop severe early-onset obesity and type 2 diabetes. Both conditions are phenocopied in mice with deleted, but whether this affects bone health remains unknown.

T-cell factor 7L2 is a novel regulator of osteoblast functions that acts in part by modulation of hypoxia signaling.

T-cell-like factor (TCF)7l2, a key effector of canonical Wnt signaling, is highly expressed in bone but nothing is known about its role in regulating osteoblast function. To test this, we generated mice with conditional disruption of gene in osteoblast lineages using floxed and -Cre mice. Skeletal parameters were evaluated using heterozygous conditional knockdown (HCKD) mice since homozygous conditional knockout died during pregnancy or immediately after birth.

Mice with Targeted Knockout of Tetraspanin 3 Exhibit Reduced Trabecular Bone Mass Caused by Decreased Osteoblast Functions.

Tetraspanin3 (TSPAN3) was identified as a binding partner of claudin11 (CLDN11) in osteoblasts and other cell types. Mice with targeted disruption of exhibited trabecular bone mass deficit caused by reduced bone formation and osteoblast function. To determine if the disruption of CLDN11 interacting protein gene results in a similar skeletal phenotype as that of knockout (KO) mice, we generated homozygous KO and heterozygous control mice and characterized their skeletal phenotypes at 13 weeks of age.

Endocuff-assisted push enteroscopy increases the detection of proximal small-bowel gastrointestinal angiodysplasias.

Gastrointestinal angiodysplasias (GIADs) are the most common causes for suspected small bowel bleeding. Fifty percent of GIADs do not need treatment due to bleeding cessation, while 45% have high re-bleeding rates, that significantly impact patient outcome and health resource utilization. We suspected that this high re-bleeding rate occurs because not all lesions are detected with present standard of care.

Repeated mild traumatic brain injury impairs fracture healing in male mice.

Objectives: The goal of this study was to evaluate the long-term impact of repeated (r) mild traumatic brain injury (mTBI) on the healing of fractures in a mouse model. Ten week-old male mice were subjected to r-mTBI once per day for 4 days followed by closed femoral fracture using a three-point bending technique, 1 week post impact and fracture healing phenotype evaluated at 20 weeks of age.

Results: Micro-CT analysis of the fracture callus region at nine weeks post fracture revealed reduced bone volume (30%, p < 0.

Computational prediction of small molecules with predicted binding to FGFR3 and testing biological effects in bone cells.

Activating anabolic receptor-mediated signaling is essential for stimulating new bone formation and for promoting bone healing in humans. Fibroblast growth factor receptor (FGFR) 3 is reported to be an important positive regulator of osteogenesis. Presently, recombinant proteins are used to stimulate FGFR3 function but have limitations for therapy due to expense and stability.

Structural insights on vitamin D receptor and screening of new potent agonist molecules: structure and ligand-based approach.

Vitamin D deficiency is one of the common clinical symptoms of severe chronic kidney disease (CKD) patients. Vitamin D receptor (VDR) is a part of the nuclear receptor family exerts vitamin D activation to maintain calcium/phosphorous homeostasis and bone metabolism. The reduction of VDR activity leads to vitamin D deficiency.

Growth Hormone Effects on Bone Loss-Induced by Mild Traumatic Brain Injury and/or Hind Limb Unloading.

Growth hormone (GH) deficiency and loss of physical activity are common features in traumatic brain injury (TBI) patients that may contribute to bone loss. Therefore, we tested the hypothesis that GH treatment will rescue the hind limb unloading (UL)-induced skeletal deficit in TBI mice. Mild TBI was induced once per day for four consecutive days.

Isolated Fluorodeoxyglucose Avid Right Pleural Deposits/Effusion on an F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Ovarian Cancer - Are they almost Certainly Metastatic? An Extrapolation of Atypical Meigs' Syndrome.

Majority of ovarian cancer (OC) patients are usually diagnosed at advanced stage and present with peritoneal spread/ascites. Some patients develop pleural deposits/effusion secondary to transdiaphragmatic spread of peritoneal disease/ascites. However, pleural deposits/effusion from OC in the absence of peritoneal disease/ascites are very rare.

Atom-based and Pharmacophore-based 3D - QSAR Studies on Vitamin D Receptor (VDR).

Aim And Objective: Vitamin D3 (1,25(OH)2D3) is a biologically active metabolite and plays a wide variety of regulatory functions in human systems. Currently, several Vitamin D analogues have been synthesized and tested against VDR (Vitamin D Receptor). Electrostatic potential methods are greatly influence the structure-based drug discovery.

Long-term Consequences of Traumatic Brain Injury in Bone Metabolism.

Traumatic brain injury (TBI) leads to long-term cognitive, behavioral, affective deficits, and increase neurodegenerative diseases. It is only in recent years that there is growing awareness that TBI even in its milder form poses long-term health consequences to not only the brain but to other organ systems. Also, the concept that hormonal signals and neural circuits that originate in the hypothalamus play key roles in regulating skeletal system is gaining recognition based on recent mouse genetic studies.

Experimental repetitive mild traumatic brain injury induces deficits in trabecular bone microarchitecture and strength in mice.

To evaluate the long-term consequence of repetitive mild traumatic brain injury (mTBI) on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at different drop heights (0.5, 1 and 1.5 m) and the skeletal phenotype was evaluated at different time points after the impact.

Mid-Esophageal Diverticulum Mimicking an Aortic Aneurysm on Chest Radiography.

Background: Mid-esophageal region is an uncommon location of esophageal diverticula, a condition usually diagnosed in elderly individuals.

Case Report: We report a case of an elderly male with incidental finding of mediastinal lesion, which was initially thought to be an aortic aneurysm. Further evaluation demonstrated a mid-esophageal diverticulum at the level of the carina.

Conditional Knockout of the MicroRNA 17-92 Cluster in Type-I Collagen-Expressing Cells Decreases Alveolar Bone Size and Incisor Tooth Mechanical Properties.

To test the role of the miR17-92 (miR) cluster in dental bones, we evaluated the incisor tooth phenotype by micro-CT in 5- and 12-week-old conditional knockout (CKO) mice deficient in the miR17-92 cluster in type-I collagen-expressing cells and bone strength by finite element analysis. The incisor teeth of CKO mice showed a 23-30 % reduction in tissue volume and bone volume. Accordingly, the stiffness and failure load of incisor teeth assessed by finite element analysis showed an 18-40 % decrease in CKO compared to wild-type mice.

Identification of novel small molecules that bind to the loop2 region of sclerostin - an in silico computational analysis.

The goal of this study was to identify small molecular weight compounds that bind to sclerostin using in-silico methods because of the established importance of sclerostin-based therapies for the treatment of disease characterized by low bone mass. The zinc database (Zdb) revealed that nine potential molecules bind to the loop2 region (functional site) of sclerostin with ADME/T properties that are within an acceptable range defined for human use. Compounds 30160056 and 56871042 showed the highest docking score.

Thyroid hormone receptor-β1 signaling is critically involved in regulating secondary ossification via promoting transcription of the Ihh gene in the epiphysis.

Thyroid hormone (TH) action is mediated through two nuclear TH receptors, THRα and THRβ. Although the role of THRα is well established in bone, less is known about the relevance of THRβ-mediated signaling in bone development. On ther basis of our recent finding that TH signaling is essential for initiation and formation of secondary ossification center, we evaluated the role of THRs in mediating TH effects on epiphysial bone formation.

Opposing effects of Sca-1(+) cell-based systemic FGF2 gene transfer strategy on lumbar versus caudal vertebrae in the mouse.

Our previous work showed that a Sca-1(+) cell-based FGF2 therapy was capable of promoting robust increases in trabecular bone formation and connectivity on the endosteum of long bones. Past work reported that administration of FGF2 protein promoted bone formation in red marrow but not in yellow marrow. The issue as to whether the Sca-1(+) cell-based FGF2 therapy is effective in yellow marrow is highly relevant to its clinical potential for osteoporosis, as most red marrows in a person of an advanced age are converted to yellow marrows.

Role of WNT16 in the regulation of periosteal bone formation in female mice.

In this study, we evaluated the role of WNT16 in regulating bone size, an important determinant of bone strength. Mice with targeted disruption of the Wnt16 gene exhibited a 24% reduction in tibia cross-sectional area at 12 weeks of age compared with that of littermate wild-type (WT) mice. Histomorphometric studies revealed that the periosteal bone formation rate and mineral apposition rate were reduced (P < .