A5060653332- Bone health and treatments
- Bone Tumor Diagnosis and Treatments
- Oral and Maxillofacial Pathology
- Bone Metabolism and Diseases
- Health and Medical Research Impacts
- Connective tissue disorders research
- Peptidase Inhibition and Analysis
- Dental Education, Practice, Research
- Inflammatory Myopathies and Dermatomyositis
- Vitamin D Research Studies
- Growth Hormone and Insulin-like Growth Factors
- Parathyroid Disorders and Treatments
- Ethics in Clinical Research
- Ubiquitin and proteasome pathways
- Biomedical Research and Pathophysiology
- Protease and Inhibitor Mechanisms
- Epigenetics and DNA Methylation
- Digestive system and related health
- Soft tissue tumor case studies
- Fibroblast Growth Factor Research
National Institute of Dental and Craniofacial Research
2020-2024
National Institutes of Health
2020-2024
Abstract Fibrous dysplasia (FD) is a rare, disabling skeletal disease for which there are no established treatments. Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand (RANKL) as potential treatment strategy. In this study, we investigated mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human pre- post-treatment phase 2 clinical trial denosumab (NCT03571191) murine...
Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a mosaic RASopathy characterized by the association of dysplastic lesions, congenital skin nevi epidermal and/or melanocytic origin, and FGF23-mediated hypophosphatemia. The primary physiological source circulating FGF23 bone cells. However, several reports have suggested lesions as excess in CSHS. Consequently, without convincing evidence efficacy, many patients with CSHS undergone painful removal cutaneous an effort to normalize blood...
Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of GNAS encoding for Gαs and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect activation the BMSC transcriptome how it influences FD lesion microenvironment are unclear. We analyzed changes induced secretome. RNAseq analysis differential gene expression cultured BMSCs from patients with healthy volunteers, an inducible mouse model FD, was...
Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants in
ABSTRACT Fibrous dysplasia (FD) is a rare mosaic disorder resulting in fractures, pain, and disability. Bone lesions appear during childhood expand skeletal growth. The rate at which FD progress the biochemical determinants of lesion formation have not been established, making it difficult to investigate implement preventative therapies. purpose this study was characterize progression children, identify clinical variables associated with progressive disease. Clinical data imaging from an...
ABSTRACT BACKGROUND Fibrous dysplasia (FD) is a rare, disabling disease with no established treatments. Growing evidence supports inhibiting the pro-osteoclastic factor receptor activator of nuclear Kappa-B ligand (RANKL) as potential treatment strategy. We conducted phase 2 trial evaluating anti-RANKL drug denosumab in adults FD, an emphasis on investigating post-discontinuation bone turnover rebound, and cellular mechanisms underlying effects FD osteoprogenitors. METHODS Eight subjects...
Fibrous dysplasia (FD) is a mosaic skeletal disorder involving the development of benign, expansile fibro-osseous lesions during childhood that cause deformity, fractures, pain, and disability. There are no well-established treatments for FD. Fibroblast activation protein (FAPα) serine protease expressed in pathological fibrotic tissues has promising clinical applications as biomarker local pro-drug activator several conditions. In this study, we explored expression
O-glycosylation is a conserved post-translational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated it glycosylates endocytic receptor megalin in kidneys, enabling proper binding reabsorption ligands, including vitamin D protein (DBP). Galnt11-deficient mice were unable to properly reabsorb DBP from urine. Vitamin plays an essential role mineral homeostasis its deficiency associated with bone...
Abstract Fibrous dysplasia (FD) is a rare, disabling skeletal disease with no established treatments. Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear Kappa-B ligand (RANKL) as potential treatment strategy. In this study, we investigated mechanisms underlying RANKL neutralization monoclonal antibody denosumab on FD osteoprogenitors, by evaluating human tissue pre- and post-treatment, in murine vivo ex pre-clinical models. Histological analysis...
Abstract Background Fibroblast growth factor receptor‐3 (FGFR3) gain‐of‐function mutations are linked to achondroplasia. Infigratinib, a FGFR1‐3 tyrosine kinase inhibitor, improves skeletal in an achondroplasia mouse model. FGFs and their receptors have critical roles developing teeth, yet effects of infigratinib on tooth development not been assessed. Dentoalveolar craniofacial phenotype Wistar rats dosed with low (0.1 mg/kg) high (1.0 dose were evaluated using micro‐computed tomography,...
In Brief: This phase 2 study investigated the effect of RANKL inhibitor denosumab on fibrous dysplasia lesion activity, as well rebound in bone turnover after treatment discontinuation.
Abstract This article, written by current student trainees within various intramural programs at the National Institutes of Health (NIH), describes how NIH experience weaves world‐class interdisciplinary research into education future oral healthcare professionals. article highlights 4 and provides perspectives from on significance their to career growth in an effort increase program awareness for faculty students, thus escalating participation predental dental students NIH. Although number...