A5018963210- Bone Metabolism and Diseases
- Bone health and treatments
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Quinazolinone synthesis and applications
- Estrogen and related hormone effects
- Nutrition, Genetics, and Disease
- Agriculture Sustainability and Environmental Impact
- Bone health and osteoporosis research
- Growth Hormone and Insulin-like Growth Factors
- Endoplasmic Reticulum Stress and Disease
- GDF15 and Related Biomarkers
- Pancreatic function and diabetes
- Glutathione Transferases and Polymorphisms
- Genomics, phytochemicals, and oxidative stress
- Cytokine Signaling Pathways and Interactions
- Diet and metabolism studies
- High Altitude and Hypoxia
- Bone and Dental Protein Studies
- Adrenal Hormones and Disorders
- Nutritional Studies and Diet
- Synthesis and Biological Activity
- Beetle Biology and Toxicology Studies
- Peptidase Inhibition and Analysis
- Advanced Machining and Optimization Techniques
Indiana University – Purdue University Indianapolis
2014-2024
Indiana University School of Medicine
2014-2024
Richard L. Roudebush VA Medical Center
2014-2024
The University of Texas MD Anderson Cancer Center
2024
University of Pittsburgh Medical Center
2023
University of Indianapolis
2019
Indiana University
2015
Clarkson University
1991
Glucocorticoid excess, either endogenous with diseases of the adrenal gland, stress, or aging when administered for immunosuppression, induces bone and muscle loss, leading to osteopenia sarcopenia. Muscle weakness increases propensity falling, which, combined lower mass, fracture risk. The mechanisms underlying glucocorticoid-induced atrophy are not completely understood. We have demonstrated that loss decreased formation, reduced strength, hallmarks glucocorticoid accompanied by...
ABSTRACT Osteocytes integrate the responses of bone to mechanical and hormonal stimuli by poorly understood mechanisms. We report here that mice with conditional deletion parathyroid hormone (PTH) receptor 1 (Pth1r) in dentin matrix protein (DMP1)-8kb–expressing cells (cKO) exhibit a modest decrease resorption leading mild increase cancellous without changes cortical bone. However, response endogenous chronic elevation PTH growing or adult cKO induced low calcium diet remained intact,...
There is an unmet need to understand the mechanisms underlying skeletal deterioration in diabetes mellitus (DM) and develop therapeutic approaches treat bone fragility diabetic patients. We demonstrate herein that mice with type 1 DM induced by streptozotocin exhibited low mass, inferior mechanical material properties, increased resorption, decreased formation, apoptosis of osteocytes, expression osteocyte-derived formation inhibitor Sost/sclerostin. Further, short treatment parathyroid...
Parathyroid hormone (PTH) affects the skeleton by acting on osteocytes (Ots) in bone through yet unclear mechanisms. We report that matrix metalloproteinase 14 (MMP14) expression/activity are increased bones from mice with genetic constitutive activation (ca) of PTH receptor 1 (PTH1R) Ots (caPTH1ROt) and exposed to elevated levels but not lacking [conditional knockout (cKO)] PTH1R (cKOPTH1ROt). Furthermore, upregulates MMP14 human cultures Ot-enriched floxed control cKOPTH1ROt mice. activity...
Accumulation of reactive oxygen species (ROS) is an important pathogenic mechanism underling the loss bone mass and strength with aging other conditions leading to osteoporosis. The transcription factor erythroid 2-related factor2 (Nrf2) plays a central role in activating cellular response ROS. Here, we examined endogenous regulated by Nrf2, its relationship architecture male female murine skeleton. Young (3 month-old) old (15 Nrf2 knockout (KO) mice either sex exhibited expected reduction...
Systemic inhibition of Notch with γ-secretase inhibitors (GSI) decreases multiple myeloma tumor growth, but the clinical use GSI is limited due to its severe gastrointestinal toxicity. In this study, we generated a inhibitor specifically directed bone (BT-GSI). BT-GSI administration decreased target gene expression in marrow, it did not alter signaling intestinal tissue or induce gut mice established human murine myeloma, treatment burden and prevented progression myeloma-induced osteolytic...
Excess of glucocorticoids (GCs) is a leading cause bone fragility, and therapeutic targets are sorely needed.We report that genetic deletion or pharmacological inhibition proline-rich tyrosine kinase 2 (Pyk2) prevents GC-induced loss by overriding GC effects detachment-induced cell apoptosis (anoikis).In wild-type vehicle-treated mice, GCs either prevented osteoclast promoted osteoblast/osteocyte apoptosis.In contrast, mice lacking Pyk2 [knockout (KO)] treated with inhibitor PF-431396 (PF)...
ABSTRACT There is an unmet need for interventions with better compliance that prevent the adverse effects of sex steroid deficiency on musculoskeletal system. We identified a blueberry cultivar (Montgomerym [Mont]) added to diet protects female mice from loss and body weight changes induced by ovariectomy. Mont, but not other blueberries, increased endogenous antioxidant response bypassing traditional transcription factor Nrf2 without activating estrogen receptor canonical signaling....
Parathyroid hormone (PTH) signaling downstream of the PTH 1 receptor (Pth1r) results in both bone anabolic and catabolic actions by mechanisms not yet fully understood. In this study, we show that Pth1r upregulates expression several components Notch pathway signals contribute to bone. We found constitutive genetic activation osteocytes (caPth1rOt) or treatment with daily increased ligands/receptors contrast, sustained elevation endogenous did change expression. Deletion sclerostin...
Despite their beneficial actions as immunosuppressants, glucocorticoids (GC) have devastating effects on the musculoskeletal and cardiac systems, long-term treated patients exhibit high incidence of falls, bone fractures, cardiovascular events. Herein, we show that GC upregulate simultaneously in bone, skeletal muscle, heart expression E3 ubiquitin ligases (atrogenes), known to stimulate proteasomal degradation proteins. Activation vitamin D receptor (VDR) signaling with VDR ligands...
The effects of acute hypoxia on regional pulmonary perfusion have been studied previously in anesthetized, artificially ventilated sheep (J. Appl. Physiol. 56: 338–342, 1984). That study indicated that a rise arterial pressure was associated with shift blood flow toward dorsal (nondependent) areas the lung. This examined relationship between pressor response and five conscious, standing ewes during 96 h normobaric hypoxia. were made hypoxic by N2 dilution an environmental chamber [arterial...
Background and Hypothesis: There is an unmet need for interventions that prevent bone loss induced by sex steroid deficiency. Loss of estrogens or androgens increases ROS in bone. We hypothesized diets containing blueberries with antioxidant properties would protect from deficiency, depending on the expression Nrf2, a transcription factor regulates endogenous response. Experimental Design: SHAM, ovariectomized (OVX), orchidectomized (ORX) 4-month-old, wild type (WT) Nrf2 knockout (KO) male...
<div>Abstract<p>Systemic inhibition of Notch with γ-secretase inhibitors (GSI) decreases multiple myeloma tumor growth, but the clinical use GSI is limited due to its severe gastrointestinal toxicity. In this study, we generated a inhibitor specifically directed bone (BT-GSI). BT-GSI administration decreased target gene expression in marrow, it did not alter signaling intestinal tissue or induce gut mice established human murine myeloma, treatment burden and prevented progression...
<p>Supplementary figures 1, 2, and 3</p>
<p>Supplementary figures 1, 2, and 3</p>