A5027073303- Bone health and osteoporosis research
- Bone health and treatments
- Bone Metabolism and Diseases
- Estrogen and related hormone effects
- Hip and Femur Fractures
- Telomeres, Telomerase, and Senescence
- Bone and Joint Diseases
- Bone fractures and treatments
- Vitamin D Research Studies
- Hormonal and reproductive studies
- Mesenchymal stem cell research
- Parathyroid Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- TGF-β signaling in diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hip disorders and treatments
- Nutrition and Health in Aging
- Advanced X-ray and CT Imaging
- Orthopaedic implants and arthroplasty
- Menopause: Health Impacts and Treatments
- Hormonal Regulation and Hypertension
- Cytokine Signaling Pathways and Interactions
- Adipokines, Inflammation, and Metabolic Diseases
- MicroRNA in disease regulation
- Sexual Differentiation and Disorders
Mayo Clinic
2016-2025
Mayo Clinic in Florida
2016-2025
Mayo Clinic in Arizona
2016-2025
WinnMed
2015-2024
University of Minnesota Rochester
2014-2024
AstraZeneca (United Kingdom)
2023
Wellcome Trust
2021
University of Göttingen
2021
Wellcome/MRC Institute of Metabolic Science
2021
University of Cambridge
2021
The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same small molecules would have tremendous impact on quality life and burden age-related chronic diseases. Here, we describe rationale for identification validation new class drugs termed senolytics, which selectively kill cells. By transcript analysis, discovered increased expression pro-survival networks in cells, consistent with their established resistance to apoptosis. Using...
Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing at etiological sites in multiple chronic diseases. Senolytics, including combination of Dasatinib Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks defend them against their own apoptotic environment. In first clinical trial senolytics, D Q improved physical function patients...
Estrogen (E) deficiency associated with the menopause is major cause of bone loss in aging women. However, men also lose significant amounts age, but they do not have equivalent menopause, and serum total testosterone (T) E levels decline only marginally age men. Thus, it has been difficult to attribute either T or deficiency. Here, we show a population-based, age-stratified sample 346 men, aged 23–90 yr, that (estradiol plus estrone) decreased over life span by 30% 12%, respectively,...
In a population-based, cross-sectional study, we assessed age- and sex-specific changes in bone structure by QCT. Over life, the area of vertebrae proximal femur increased approximately 15% both sexes, whereas vBMD at these sites decreased 39-55% 34-46%, respectively, with greater decreases women than men.The density aging that lead to fragility fractures are still unclear.In an sex-stratified population sample 373 323 men (age, 20-97 years), geometry volumetric BMD (vBMD) QCT lumbar spine,...
Abstract Osteoporosis is a serious complication of systemic glucocorticoid use. However, while glucocorticoids increase bone resorption in vitro and vivo, the mechanism(s) this effect are at present unclear. Recent studies have identified osteoprotegerin (OPG) ligand (OPG-L) as final effector osteoclastogenesis, an action that opposed by soluble neutralizing receptor, OPG. Thus, we assessed regulation OPG OPG-L various human osteoblastic lineage cells using Northern analysis, RT-PCR, ELISA....
Young adult males who cannot produce or respond to estrogen (E) are osteopenic, suggesting that E may regulate bone turnover in men, as well women. Both bioavailable and testosterone (T) decrease substantially aging but it is unclear which deficiency the more important factor contributing increased resorption impaired formation leads their loss. Thus, we addressed this issue directly by eliminating endogenous T production 59 elderly men (mean age 68 years), studying them first under...
Both bone mass and serum leptin levels are increased in obesity. Because osteoblasts adipocytes arise from a common precursor marrow, we assessed the effects of human recombinant on conditionally immortalized marrow stromal cell line, hMS2–12, with potential to differentiate either osteoblast or adipocyte phenotypes. By RT-PCR Western immunoblot analysis, hMS2–12 cells expressed messenger RNA (mRNA) protein for receptor. Leptin did not affect proliferation, but resulted dose- time-dependent...
Studies in rodents have implicated various cytokines as paracrine mediators of increased osteoclastogenesis during estrogen deficiency, but increases RANKL, the final effector osteoclastogenesis, not been demonstrated. Thus, we isolated bone marrow mononuclear cells expressing RANKL on their surfaces by two-color flow cytometry using FITC-conjugated osteoprotegerin-Fc (OPG-Fc-FITC) a probe. The were characterized preosteoblastic stromal (MSCs), T lymphocytes, or B lymphocytes Ab's against...
Studies in rodents have implicated various cytokines as paracrine mediators of increased osteoclastogenesis during estrogen deficiency, but increases RANKL, the final effector osteoclastogenesis, not been demonstrated. Thus, we isolated bone marrow mononuclear cells expressing RANKL on their surfaces by two-color flow cytometry using FITC-conjugated osteoprotegerin-Fc (OPG-Fc-FITC) a probe. The were characterized preosteoblastic stromal (MSCs), T lymphocytes, or B lymphocytes Ab’s against...
The identity of the paracrine mediator(s) antiresorptive action estrogen on bone cells is controversial. Osteoprotegerin (OPG) was recently identified as a soluble member tumor necrosis factor (TNF) receptor (TNF-R) superfamily that secreted by osteoblast lineage and acts binding to neutralizing its cognate ligand, OPG-L, required for osteoclastogenesis. OPG prevents loss when administered ovariectomized rats, induces osteoporosis ablated in knock-out mice, osteopetrosis overexpressed...