A5025670982- Bone Metabolism and Diseases
- Bone health and osteoporosis research
- Gut microbiota and health
- Digestive system and related health
- Bone health and treatments
- Vitamin D Research Studies
- Bone Tissue Engineering Materials
- Bone and Dental Protein Studies
- TGF-β signaling in diseases
- Inflammatory Bowel Disease
- Orthopaedic implants and arthroplasty
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- COVID-19 Clinical Research Studies
- Diet and metabolism studies
- Bone and Joint Diseases
- Microscopic Colitis
- Probiotics and Fermented Foods
- Alkaline Phosphatase Research Studies
- Diabetes and associated disorders
- Receptor Mechanisms and Signaling
- Helicobacter pylori-related gastroenterology studies
- Cell Adhesion Molecules Research
- Clostridium difficile and Clostridium perfringens research
- Long-Term Effects of COVID-19
Michigan State University
2014-2024
Guy's and St Thomas' NHS Foundation Trust
2024
St Thomas' Hospital
2024
Tallaght University Hospital
2022
Michigan United
2015-2017
Mater Misericordiae University Hospital
2015-2017
Microchips Biotech (United States)
2012
Laboratoire d’Imagerie Biomédicale
2011
University of Nebraska Medical Center
2003-2004
University of Waterloo
2001
The AML/CBFA family of runt homology domain (rhd) transcription factors regulates expression mammalian genes the hematopoietic lineage. AML1, AML2, and AML3 are three AML identified to date which influence myeloid cell growth differentiation. Recently, AML-related proteins were in an osteoblast-specific promoter binding complex that functionally modulates bone-restricted osteocalcin gene. In present study we demonstrate primary rat osteoblasts AML-3 is member complex. Antibody specific for...
Estrogen deficiency is a major risk factor for osteoporosis that associated with bone inflammation and resorption. Half of women over the age 50 will experience an related fracture in their lifetime, thus novel therapies are needed to combat post-menopausal loss. Recent studies suggest important role gut-bone signaling pathways microbiota regulating health. Given bacterium Lactobacillus reuteri ATCC PTA 6475 (L. reuteri) secretes beneficial immunomodulatory factors, we examined if this...
The first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1-34) [hPTH(1-34)] was delivered from the in vivo. hPTH(1-34) only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance obstacle to effective treatment. Furthermore, a net increase bone mineral density intermittent or pulsatile delivery, challenge for products. devices, containing discrete doses lyophilized hPTH(1-34),...
Abstract Osteoporosis can result from intestinal inflammation, as is seen with inflammatory bowel disease. Probiotics, microorganisms that provide a health benefit to the host when ingested in adequate amounts, have anti‐inflammatory properties and are currently being examined treat Here, we if treating healthy male mice Lactobacillus reuteri ATCC PTA 6475 (a candidate probiotic anti‐TNFα activity) could affect TNFα levels enhance bone density. Adult were given L. orally by gavage for...
ABSTRACT Glucocorticoids (GCs) are potent immune-modulating drugs with significant side effects, including glucocorticoid-induced osteoporosis (GIO). GCs directly induce osteoblast and osteocyte apoptosis but also alter intestinal microbiota composition. Although the gut is known to contribute regulation of bone density, its role in GIO has never been examined. To test this, male C57/Bl6J mice were treated for 8 weeks GC (prednisolone, GC-Tx) presence or absence broad-spectrum antibiotic...
Antibiotic treatment, commonly prescribed for bacterial infections, depletes and subsequently causes long-term alterations in intestinal microbiota composition. Knowing the importance of microbiome regulation bone density, we investigated effect postantibiotic treatment on gut health. Intestinal repopulation at 4-weeks resulted an increase Firmicutes:Bacteroidetes ratio, increased permeability, notably reduced femoral trabecular volume (approximately 30%, p < 0.01). Treatment with a mucus...
Insulin-dependent diabetes mellitus (IDDM) is associated with increased risk of osteopenia/osteoporosis in humans. The mechanisms accounting for diabetic bone loss remain unclear. Pharmacologic inducers IDDM, such as streptozotocin, mimic key aspects rodents, allow analysis at the onset diabetes, and induce genetically modified mice. However, side effects unrelated to can complicate data interpretation. nonobese (NOD) mouse model develops spontaneously without external influences, negating...
Abstract Insulin dependent diabetes mellitus (IDDM; type I) is a chronic disease stemming from little or no insulin production and elevated blood glucose levels. IDDM associated with osteoporosis increased fracture rates. The mechanisms underlying bone loss are not known. Previously we demonstrated that osteoblasts exhibit response to acute (1 24 h) hyperglycemia hyperosmolality. Here examined the influence of (30 mM) its hyperosmolality on osteoblast phenotype. Our findings demonstrate...
Decreased bone mass, osteoporosis, and increased fracture rates are common skeletal complications in patients with insulin-dependent diabetes mellitus (IDDM; type I diabetes). IDDM develops from little or no insulin production is marked by elevated blood glucose levels weight loss. In this study we use a streptozotocin-induced diabetic mouse model to examine the effect of on bone. Histology microcomputed tomography demonstrate that adult mice, exhibiting plasma osmolality, have decreased...
Developmental studies of oncogene expression implicate the Fos and Jun family transcription factors in regulation bone growth differentiation. Promoters many developmentally regulated genes, including osteocalcin, a marker osteoblast differentiation, contain AP-1 sites that bind Fos/Jun dimers. Here, we demonstrate selective fos- jun-related genes is functionally related to stage differentiation vitro. During proliferation, nuclear protein levels all seven activating protein-1 (AP-1) members...
Type 1 diabetes (T1D)–induced osteoporosis is characterized by a predominant suppression of osteoblast number and activity, as well increased bone marrow adiposity but no change in osteoclast activity. The fundamental mechanisms alternative anabolic treatments (with few side effects) for T1D loss remain undetermined. Recent studies our laboratory others indicate that probiotics can benefit health. Here, we demonstrate Lactobacillus reuteri, probiotic with anti-inflammatory health properties,...
As many as 50% of adults with type I (T1) diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent and/or restore lost in T1 diabetic patients requires knowledge the molecular mechanisms accounting pathology. Because cell culture models alone cannot fully address systemic/metabolic complexity diabetes, animal critical. A variety exist including spontaneous pharmacologically induced rodents. In this paper, we discuss streptozotocin (STZ)-induced...
Background & Aims We previously demonstrated that short-term oral administration of the probiotic Lactobacillus reuteri 6475 enhanced bone density in male but not female mice. also established L. health and prevented loss estrogen-deficient In this study, we tested whether a mild inflammatory state and/or long-term treatment with was required to promote positive effect estrogen-sufficient Methods A induced mice by dorsal surgical incision (DSI). Following DSI animals were orally supplemented...
Abstract Hydroxyapatite describes both the natural mineral phase of bone as well widely used calcium–phosphate implant substitute. Given that hydroxyapatite is a major component in vivo surface with which osteoblasts interact, it surprising most studies examining regulation osteoblast growth and differentiation utilize plastic surfaces. Here we demonstrate phenotype mouse MC3T3‐E1 significantly altered on compared Specifically, alkaline phosphatase activity messenger RNA levels, markers...
This study examines the mechanism by which TGF-beta 1, an important mediator of cell growth and differentiation, blocks differentiation normal rat diploid fetal osteoblasts in vitro. We have established that inability for pre-osteoblasts to differentiate is associated with changes expression growth, matrix forming, bone related genes. These include histone, jun B, c-fos, collagen, fibronectin, osteocalcin, alkaline phosphatase, osteopontin. Morphologically, 1-treated exhibit elongated,...
The OC box of the rat osteocalcin promoter (nt -99 to -76) is principal proximal regulatory element contributing both tissue-specific and developmental control gene expression. central motif includes a perfect consensus DNA binding site for certain homeodomain proteins. Homeodomain proteins are transcription factors that direct proper development by regulating specific temporal spatial patterns We therefore addressed role in activity promoter. In this study, combined application mutagenesis...
Abstract Bone mineral contains hydroxyapatite (HA). This is the surface that mature osteoblasts and osteocytes interact with. Synthetic HA widely used in orthopedic surgeries as an implant or coating. The bone‐like surfaces increase union bone formation; however, mechanisms accounting for this effect on are not known. In study, we compared gene expression profiles of responding to plastic 24 h. Expression were also between discs processed with gravity‐sieved combined gravity air‐jet‐sieved...
Abstract Diabetes type I is associated with bone loss and increased adiposity. Osteoblasts adipocytes are both derived from mesenchymal stem cells located in the marrow, therefore we hypothesized that if could block adipocyte differentiation might prevent diabetic mice. Control insulin‐deficient BALB/c mice were chronically treated a peroxisomal proliferator‐activated receptor γ (PPARγ) antagonist, bisphenol‐A‐diglycidyl ether (BADGE), to differentiation. Effects on density, adiposity, gene...