A5077283095- Bone Metabolism and Diseases
- Bone health and treatments
- Bone health and osteoporosis research
- Estrogen and related hormone effects
- Cytokine Signaling Pathways and Interactions
- Inflammatory mediators and NSAID effects
- Reproductive System and Pregnancy
- Vitamin D Research Studies
- Gut microbiota and health
- Bone and Joint Diseases
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Parathyroid Disorders and Treatments
- Fibroblast Growth Factor Research
- Advanced X-ray and CT Imaging
- TGF-β signaling in diseases
- Diet and metabolism studies
- Metabolism and Genetic Disorders
- Endometriosis Research and Treatment
- Digestive system and related health
- Psoriasis: Treatment and Pathogenesis
- Mesenchymal stem cell research
- Epigenetics and DNA Methylation
- Wnt/β-catenin signaling in development and cancer
- Bone and Dental Protein Studies
Emory University
2015-2024
Barnes-Jewish Hospital
1996-2011
Mallinckrodt (United States)
2011
Shriners Hospitals for Children - Erie
2011
Augusta University
2011
Istituto Superiore di Sanità
2004-2007
Georgia Institute of Technology
2004
Howard Hughes Medical Institute
2004
Yale University
2004
Washington University in St. Louis
1992-2003
Estrogen deficiency induces bone loss by upregulating osteoclastogenesis mechanisms not completely defined. We found that ovariectomy-enhanced T-cell production of TNF-α, which, acting through the TNF-α receptor p55, augments macrophage colony-stimulating factor–induced (M-CSF–induced) and RANKL-induced osteoclastogenesis. Ovariectomy failed to induce loss, stimulate resorption, or increase M-CSF– RANKL-dependent in deficient mice, establishing T cells as essential mediators bone-wasting...
Although recent epidemiological studies found a positive correlation between dietary vitamin C intake and bone mineral density, data on plasma levels of or other antioxidants in osteoporotic subjects are scanty. The aim this study was to evaluate whether antioxidant defenses decreased elderly women and, if is the case, understand osteoporosis condition characterized by increased oxidative stress. To answer these questions, vitamins C, E, A; uric acid; enzymatic activities superoxide...
A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, deficiency increased gut permeability, expanded Th17 cells, upregulated osteoclastogenic cytokines TNFα (TNF), RANKL, IL-17 small intestine BM. germ-free (GF) mice, failed increase cytokine production, stimulate...
In vivo studies have shown T cells to be central the mechanism by which estrogen deficiency induces bone loss, but involved remains, in part, undefined. vitro , from ovariectomized mice produce increased amounts of tumor necrosis factor (TNF), augments receptor activator NF-κB ligand (RANKL)-induced osteoclastogenesis. However, both and relevance this phenomenon remain established. study, we found that ovariectomy number marrow cell-producing TNF without altering production per cell....
T cell–produced cytokines play a pivotal role in the bone loss caused by inflammation, infection, and estrogen deficiency. IFN-γ is major product of activated helper cells that can function as pro- or antiresorptive cytokine, but reason why has variable effects unknown. Here we show blunts osteoclast formation through direct targeting precursors indirectly stimulates promotes resorption stimulating antigen-dependent cell activation secretion osteoclastogenic factors RANKL TNF-α. Analysis...
Nutritional supplementation with probiotics can prevent pathologic bone loss. Here we examined the impact of Lactobacillus rhamnosus GG (LGG) on homeostasis in eugonadic young mice. Micro-computed tomography revealed that LGG increased trabecular volume mice, which was due to formation. Butyrate produced gut following ingestion, or butyrate fed directly germ-free induced expansion intestinal and marrow (BM) regulatory T (Treg) cells. Interaction BM CD8
The differentiation of cells the monocytic lineage into mature osteoclasts (OC) is specifically induced by tumor necrosis factor-related factor, RANKL (receptor activator NF-κB ligand; also known as OPGL, ODF, or TRANCE). Because inhibition osteoclastogenesis one main mechanisms which estrogen (E2) prevents bone loss, it likely that E2 may regulate either production of, target cell responsiveness to RANKL. We found decreases OC both murine marrow monocytes and RAW 264.7 cells, a line,...
Osteoporosis is a state of reduced skeletal mass characterized by various rates bone remodeling. Multiple locally elaborated factors have been identified that appear to influence the cellular events in The possible role(s) these pathogenesis osteoporosis unknown. One such factor, interleukin 1 (IL-1), particular interest, as this protein known stimulate resorption and perhaps formation. Consequently, we measured spontaneous secretion IL-1 activity cultured peripheral blood monocytes obtained...
Expansion of the pool tumor necrosis factor (TNF)-α-producing T cells is instrumental for bone loss induced by estrogen deficiency, but responsible mechanism unknown. Here we show that ovariectomy up-regulates IFN-γ-induced class II transactivator, a multitarget immune modulator, resulting in increased antigen presentation macrophages, enhanced cell activation, and prolonged lifespan active cells. Up-regulation transactivator derives from production IFN-γ helper 1 cells, secretion IL-12...
IL-7, a powerful lymphopoietic cytokine, is elevated in rheumatoid arthritis (RA) and known to induce bone loss when administered vivo . IL-7 has been suggested loss, part, by stimulating the proliferation of B220 + cells, population capable acting as early osteoclast (OC) precursors. However, mechanism which leads differentiation precursors into mature OCs remains unknown. We previously reported that, vitro , up-regulated T cell cytokines including receptor activator nuclear factor κB...
To analyze how estrogen blocks osteoclastogenesis, we investigated the effects of ovariectomy on osteoclast (OC) formation in co-cultures purified OC precursors and stromal cells (SC). was higher containing SC from ovariectomized mice than those sham-operated mice, thus suggesting that regulates osteoclastogenesis by targeting SC. Ovariectomy also increased mononuclear cell secretion interleukin (IL)-1) tumor necrosis factor (TNF) production macrophage colony-stimulating (MCSF)....
Central to the bone-sparing effect of estrogen (E2) is its ability block monocytic production osteoclastogenic cytokine TNF-α (TNF). However, mechanism by which E2 downregulates TNF presently unknown. Transient transfection studies in HeLa cells, an receptor–negative line, suggest that inhibits gene expression through mediated receptor β (ERβ). We also report RAW 264.7 receptor–positive murine cytokine-induced decreasing activity Jun NH2-terminal kinase (JNK). The resulting diminished...
Abstract Considerable evidence supports the hypothesis that estrogen prevents bone loss by blocking marrow cell production of pro-osteoclastogenic cytokines. However, controversy remains on role candidate factors, such as tumor necrosis factor (TNF) and interleukin-6 (IL-6). To investigate contribution these cytokines to pathogenesis ovariectomy (OVX)-induced loss, OVX mice were treated with either TNF binding protein (TNFbp), an inhibitor TNF, anti–(IL-6) antibody (Ab) 20F3, or for first 2...
Interleukin-1 (IL-1), a cytokine produced by bone marrow cells and cells, has been implicated in the pathogenesis of postmenopausal osteoporosis because its potent stimulatory effects on resorption vitro vivo. To investigate whether IL-1 plays direct causal role post ovariectomy loss, 6-mo-old ovariectomized rats were treated with subcutaneous infusions receptor antagonist (IL-1ra), specific competitor IL-1, for 4 wk, beginning either at time surgery or wk after ovariectomy. The density...
Postmenopausal bone loss stems from the inability of osteoblastic activity to match increase in osteoclastic resorption induced by estrogen deficiency. However, mechanism that uncouples osteoblast osteoclast activities remains unexplained. We show ovariectomy enhances production osteoclastogenic cytokine IL-7, and its neutralization vivo prevents ovariectomy-induced loss. Surprisingly, serum osteocalcin levels, a biochemical marker formation, suggested bone-sparing effects IL-7 were due not...
Postmenopausal bone loss stems from the inability of osteoblastic activity to match increase in osteoclastic resorption induced by estrogen deficiency. However, mechanism that uncouples osteoblast osteoclast activities remains unexplained. We show ovariectomy enhances production osteoclastogenic cytokine IL-7, and its neutralization vivo prevents ovariectomy-induced loss. Surprisingly, serum osteocalcin levels, a biochemical marker formation, suggested bone-sparing effects IL-7 were due not...
Central to the pathogenesis of osteoporosis is ability estrogen deficiency increase osteoclast formation by enhancing stromal cell production osteoclastogenic cytokine macrophage colony-stimulating factor (M-CSF). We report that cells from ovariectomized mice exhibit increased casein kinase II-dependent phosphorylation nuclear protein Egr-1. Phosphorylated Egr-1 binds less avidly transcriptional activator Sp-1 and resulting higher levels free stimulate transactivation M-CSF gene. Estrogen...
The bone loss induced by ovariectomy (ovx) has been linked to increased production of osteoclastogenic cytokines marrow cells, including T cells and stromal (SCs). It is presently unknown whether regulatory interactions between these lineages contribute the effects ovx in bone, however. Here, we show that T-cell costimulatory molecule CD40 ligand (CD40L) required for expand SCs; promote osteoblast proliferation differentiation; regulate SC factors macrophage colony-stimulating factor,...
Increased production of tumor necrosis factor alpha (TNF) in the bone marrow (BM) response to both oxidative stress and T cell activation contributes loss induced by estrogen deficiency, but it is presently unknown whether causes through cells. Here we show that ovariectomy an accumulation BM reactive oxygen species, which leads increased TNF activated cells up-regulation costimulatory molecule CD80 on dendritic Accordingly, prevented treatment ovariectomized mice with either antioxidants or...