A5047944812- Bone health and treatments
- Bone Metabolism and Diseases
- Fibroblast Growth Factor Research
- Parathyroid Disorders and Treatments
- Osteoarthritis Treatment and Mechanisms
- Bone health and osteoporosis research
- Connective tissue disorders research
- RNA Research and Splicing
- Bone and Joint Diseases
- Bone fractures and treatments
- Bone Tissue Engineering Materials
- RNA Interference and Gene Delivery
- Cancer Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Proteoglycans and glycosaminoglycans research
- RNA modifications and cancer
- NF-κB Signaling Pathways
- Orthopaedic implants and arthroplasty
- Cytokine Signaling Pathways and Interactions
- Metabolism, Diabetes, and Cancer
- Cell death mechanisms and regulation
- Graphene and Nanomaterials Applications
- Periodontal Regeneration and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Neurogenetic and Muscular Disorders Research
McGill University
2011-2025
McGill University Health Centre
2013-2025
Montreal General Hospital
1988-2017
Cancer Institute (WIA)
2015
University College London
2015
Parkland Health & Hospital System
2014
Dean College
2007
Montreal Children's Hospital
2006
Jewish General Hospital
1995-2005
Niigata University
2003-2005
To elucidate the role of PTHrP in skeletal development, we examined proximal tibial epiphysis and metaphysis wild-type (PTHrP-normal) 18-19-d-old fetal mice chondrodystrophic litter mates homozygous for a disrupted allele generated via homologous recombination embryonic stem cells (PTHrP-depleted). In PTHrP-normal epiphysis, immunocytochemistry showed to be localized chondrocytes within resting zone at junction between proliferative hypertrophic zones. PTHrP-depleted epiphyses, diminished...
Parathyroid hormone-related peptide (PTHrP) is a mediator of cellular growth and differentiation as well cause malignancy-induced hypercalcemia. Most the actions PTHrP have been attributed to its interaction with specific cell surface receptor that binds N-terminal domain protein. Here we present evidence promotes some effects by translocating nucleolus. Localization transiently expressed nucleolus was dependent on presence highly basic region at carboxyl terminus molecule bears homology...
Mdm2 is required to negatively regulate p53 activity at the peri-implantation stage of early mouse development. However, absolute requirement for throughout embryogenesis and in organogenesis unknown. To explore Mdm2–p53 signaling osteogenesis, Mdm2-conditional mice were bred with Col3.6-Cre–transgenic that express Cre recombinase osteoblast lineage cells. Col3.6-Cre die birth display multiple skeletal defects. Osteoblast progenitor cells deleted have elevated activity, reduced...
Signaling by fibroblast growth factor (FGF) 18 and FGF receptor 3 (FGFR3) have been shown to regulate proliferation, differentiation, matrix production of articular plate chondrocytes <i>in vivo</i> vitro</i>. Notably, the congenital absence either FGF18 or FGFR3 resulted in similar expansion plates fetal mice addition human culture enhanced proliferation production. Based on these other experiments it has proposed that signals through promote cartilage chondrocytes. Its role chondrogenesis...
Oculodentodigital dysplasia (ODDD) is an autosomal dominant disorder characterized by pleiotropic developmental anomalies of the limbs, teeth, face and eyes that was shown recently to be caused mutations in gap junction protein alpha 1 gene (GJA1), encoding connexin 43 (Cx43). In course performing N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutation exhibits many classic symptoms ODDD, including syndactyly, enamel hypoplasia, craniofacial cardiac dysfunction. Positional...
Fibroblast growth factors play important roles in angiogenesis, but their functions lymphangiogenesis remain poorly understood. The homeodomain transcription factor Prox1 is essential for development of the lymphatic system by specifying endothelial cell (LEC) fate. Here, we identify fibroblast (FGF) receptor (FGFR)-3 as a novel target gene. Ectopic overexpression blood vascular cells up-regulates FGFR-3. induces expression IIIc isoform, which also found to be major isoform FGFR-3 expressed...
PTH-like peptide (PLP) is produced by tumors commonly associated with hypercalcemia as well nonneoplastic tissues and several endocrine glands tumors. To characterize the distribution of PLP in human tumors, we localized formalin-fixed paraffin-embedded material using avidin-biotin-peroxidase technique polyclonal antisera. Among hormone-producing tissues, was identified nontumorous adenohypophysis pituitary adenomas; medullary thyroid carcinomas; normal, hyperplastic, adenomatous...
We have examined circulating concentrations of a parathyroid hormone-like peptide (PLP) in patients with malignancies and hyperparathyroidism. The radioimmunoassay employed reacts synthetic amino-terminal fragments PLP but not hormone. Elevated plasma were observed 50% malignancy hypercalcemia 15% normocalcemic cancer patients, mean values being higher the former group. Detectable found 2 39 control subjects. In breast declined concomitantly reduction tumor burden. Adenocarcinoma squamous...
Mutations in the PEX gene are responsible for X-linked hypophosphatemic rickets. To gain insight into role of normal physiology we have cloned human full-length cDNA and studied its tissue expression, subcellular localization, peptidase activity. We show that encodes a 749-amino acid protein structurally related to family neutral endopeptidases include neprilysin as prototype. By Northern blot analysis, size transcript is 6.5 kilobases. determined by semi-quantitative polymerase chain...
We have examined the expression and secretion of endogenous parathyroid hormone-like peptide (PLP) in primary cultures normal human keratinocytes. In response to growth factors fetal bovine serum, PLP mRNA immunoreactive release into conditioned medium was rapidly increased (within hours) whereas these effects were inhibited by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. These early responses not influenced raising calcium concentration from 0.15 1.0 mM. contrast, increasing mM, addition...
Mutations that cause constitutive activation of fibroblast growth factor receptor 3 (FGFR3) result in skeletal disorders are characterized by short-limbed dwarfism and premature closure cranial sutures. In previous work, it was shown congenital deficiency FGFR3 led to overgrowth. Using a combination imaging, classic histology molecular cell biology we now show young adult FGFR3−/− mice osteopenic due reduced cortical bone thickness defective trabecular mineralization. The reduction...
In previous work we showed that the chondrodysplastic phenotype of mice homozygous for a null mutation PTH-related peptide (PTHrP) gene was due in part to reduced proliferation and aberrant differentiation growth plate chondrocytes. present study have extended those observations by examining chondrocytes evidence PTH/PTHrP receptor expression, proliferation, programmed cell death. Receptor messenger RNA protein were expressed resting proliferative zones both wild-type mutant mice. normal...
The Src substrate associated in mitosis of 68 kDa (Sam68) is a KH-type RNA binding protein that has been shown to regulate several aspects metabolism; however, its physiologic role remained elusive. Herein we report the generation Sam68-null mice by homologous recombination. Aged Sam68-/- preserved their bone mass, sharp contrast with 12-month-old wild-type littermates which mass was decreased up approximately 75%. In fact, volume virtually indistinguishable from 4-month-old or mice. marrow...
Most fundamental studies in cartilage tissue engineering investigate the ability of chondrocytes from young animals to produce cartilaginous matrix under various conditions, while current clinical applications such as autologous chondrocyte implantation, use donors that are decades past skeletal maturity. Previous investigations have suggested several characteristics primary age-dependent but none quantified cell proliferation, proteoglycan synthesis and accumulation, collagen compressive...
PTH-like peptide (PLP) is produced by a number of tumors commonly associated with the development hypercalcemia. Analysis expression PLP gene has demonstrated that variety nonneoplastic endocrine and nonendocrine tissues contain mRNA transcripts. Using combination Northern blot analysis, immunohistochemistry, RIAs, we have expressed in normal human rat fetal adult islets Langerhans. was not confined to cells containing single pancreatic islet hormone, but found all four major subtypes....
Abstract Infiltration of bone marrow with fat is a prevalent feature in people age-related loss and osteoporosis, which correlates inversely formation positively high expression levels peroxisomal proliferator-activated receptor gamma (PPARγ). Inhibition PPARγ thus represents potential therapeutic approach for loss. In this study, we examined the effect inhibition on skeletally mature C57BL/6 male mice. Nine-month-old mice were treated antagonist, bisphenol-A-diglycidyl ether (BADGE), alone...
Background: This study aimed at investigating the prolonged effects of glucocorticoids and bisphosphonates on bone. Methods: Six-to-eight-month-old skeletally mature male Sprague Dawley rats were randomized to receive a cancer therapy combination zoledronic acid (ZA = 0.13 mg/kg) dexamethasone (DX 3.8 (treatment group, n 10) or sterile phosphate buffer saline solution (control 10). The received weekly intraperitoneal injections for 8 weeks, which stopped 6 weeks before euthanasia....
Abstract Vitamin D deficiency results in defects endochondral bone development characteristic of rickets, which include elongation the cartilaginous growth plates and disorganization primary spongiosa. These are caused part by impaired cartilage mineralization vascularization chondro‐osseous junction. Blood vessel invasion mineralized is an essential step ossification, providing access for cells that degrade as well those form bone. Vascular endothelial factor (VEGF) was shown to be a key...
Parathyroid hormone-related protein (PTHrP) is a secreted that acts as an autocrine and paracrine mediator of cell proliferation differentiation. In addition to its biological activity mediated through signal transduction cascades, there evidence for intracellular role PTHrP in cycle progression apoptosis. These effects are mid-region nuclear targeting sequence (NTS) localizes the region nucleolus where ribonucleoprotein complexes form vivo. this work, we show endogenous, transfected, andin...
Previous work has identified the parathyroid hormone-related protein (PTHrP) nucleolar targeting signal (NTS) as both necessary and sufficient for localization of PTHrP to nucleus nucleolus a variety cells where it is believed participate in regulation cell proliferation, differentiation, apoptotic death. The mechanism whereby secreted peptide, such PTHrP, gains access nuclear compartment remains question debate. current examines possibility that exogenous internalized transported by...
Abstract A patient with classic clinical and biochemical features of tumor-induced osteomalacia (hypophosphatemia, phosphaturia, undetectable serum concentrations 1,25-dihydroxyvitamin D [1,25(OH)2D]) was studied before after resection a benign extraskeletal chondroma from the plantar surface foot. Presurgical laboratory evaluation notable for normal calcium, intact parathyroid hormone (PTH), hormone-related protein (PTHrP), osteocalcin, increased alkaline phosphatase activity, frankly...