A5041908437- Bone Metabolism and Diseases
- Wnt/β-catenin signaling in development and cancer
- Muscle Physiology and Disorders
- Spine and Intervertebral Disc Pathology
- Bone health and osteoporosis research
- Bone health and treatments
- Connective tissue disorders research
- Sarcoma Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Musculoskeletal pain and rehabilitation
- Healthcare and Venom Research
- Neurofibromatosis and Schwannoma Cases
- Cytokine Signaling Pathways and Interactions
- Plant Toxicity and Pharmacological Properties
- Protein Kinase Regulation and GTPase Signaling
- Cardiomyopathy and Myosin Studies
- Dermatological and Skeletal Disorders
- Peripheral Nerve Disorders
- Genetics and Physical Performance
- Bone and Dental Protein Studies
- Adipose Tissue and Metabolism
- Cancer, Lipids, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Advanced MRI Techniques and Applications
- Diet, Metabolism, and Disease
Indiana University – Purdue University Indianapolis
2009-2024
Indiana University School of Medicine
2008-2024
University of Pennsylvania
2018
Purdue University West Lafayette
2007-2015
University of Indianapolis
2009
Sclerostin, the protein product of Sost gene, is a potent inhibitor bone formation. Among cells, sclerostin found nearly exclusively in osteocytes, cell type that historically has been implicated sensing and initiating mechanical signaling. The recent discovery antagonistic effects on Lrp5 receptor signaling, crucial mediator skeletal mechanotransduction, provides potential mechanism for osteocytes to control by adjusting their (Wnt inhibitory) signal output modulate Wnt signaling effector...
Autosomal dominant osteopetrosis (ADO) is a rare genetic disorder resulting from impaired osteoclastic bone resorption. Clinical manifestations frequently include fractures, osteonecrosis (particularly of the jaw or maxilla), osteomyelitis, blindness, and/or marrow failure. ADO usually results heterozygous missense variants in Chloride Channel 7 gene (CLCN7) that cause disease by negative mechanism. Variants T-cell immune regulator 1 (TCIRG1) are commonly identified autosomal recessive but...
Intracellular signals involved in the maturation and function of osteoclasts are poorly understood. Here, we demonstrate that express multiple regulatory subunits class I(A) phosphatidylinositol 3-kinase (PI3-K) although expression full-length form p85alpha is most abundant. In vivo, deficiency results a significantly greater number trabeculae lower spacing between as well increased bone mass both males females compared to their sex-matched wild-type controls. Consistently, p85alpha(-/-)...
The low density lipoprotein receptor-related protein-5 (LRP5), a co-receptor in the Wnt signaling pathway, modulates bone mass humans and mice. Lrp5 knock-out mice have severely impaired responsiveness to mechanical stimulation whereas gain-of-function knock-in transgenic enhanced stimulation. Those observations highlight importance of protein cell mechanotransduction. It is unclear if how high mass-causing (HBM) point mutations alter bone-wasting effects disuse. To address this issue we...
Abstract Certain missense mutations affecting LRP5 cause high bone mass (HBM) in humans. Based on vitro evidence, HBM receptors are thought to exert their effects by providing resistance binding/inhibition of secreted inhibitors such as sclerostin (SOST) and Dickkopf homolog-1 (DKK1). We previously reported the creation two Lrp5 knock-in mouse models, which human p.A214V or p.G171V were knocked into endogenous locus. To determine whether mice resistant SOST- DKK1-induced osteopenia, we bred...
The osteo-anabolic effects of intermittent parathyroid hormone (PTH) treatment require insulin-like growth factor (IGF) signaling through the IGF-I receptor. A major downstream target receptor (via Akt) is mammalian rapamycin (mTOR), a kinase involved in protein synthesis. We investigated whether bone-building PTH functional mTOR signaling. Mice were treated with daily 1-34 (0, 10, 30, or 90 microg/kg) for 6 weeks presence absence rapamycin, selective inhibitor mTOR. found that all doses...
Intervertebral disc (IVD) degeneration is a leading cause of low back pain, characterized by accelerated extracellular matrix breakdown and IVD height loss, but there no approved pharmacological therapeutic. Deletion Wnt ligand competitor Lrp5 induces degeneration, suggesting that signaling essential for homeostasis. Therefore, the may respond to neutralization competitors sost(gene)/sclerostin(protein) and/or dickkopf-1 (dkk1). Anti-sclerostin antibody (scl-Ab) an FDA-approved bone...
The osteopetroses are a group of rare genetic diseases caused by osteoclast dysfunction or absence. hallmark osteopetrosis is generalized increased bone mineral density (BMD). However, the fragile and fractures common. Autosomal recessive usually severe disorder often life-threatening in childhood. We present male siblings with autosomal due to biallelic variants TCIRG1 who survived childhood underwent hematopoietic stem cell transplant (HSCT) adulthood. One sibling died posttransplant...
Abstract Estrogen agonist raloxifene is an FDA-approved treatment for osteoporosis in postmenopausal women that may also be a promising prophylactic painful intervertebral disc (IVD) degeneration. Here, we hypothesized would augment IVD structure and reduce neurokinin-1 (substance P) young old mice by stimulating estrogen signaling. 2.5 month (male female) 22.5 (female) C57Bl/6J were subcutaneously injected with hydrochloride (5x/week, 6week, n=7-9/grp). Next, to determine the impact of...
The low‐density‐lipoprotein receptor‐related protein 5 (LRP5), a co‐receptor in the Wnt signaling pathway, has been implicated as an important modulator of bone mass. Among humans, loss function mutation LRP5 results severe osteoporotic disease, while certain missense mutations gene result high mass (HBM) phenotype. To explore role HBM skeletal development and function, we have inserted (knocked‐in) two mutations, A214V G171V, into mice. We measured areal mineral density (aBMD) vivo from 4.5...
Abstract Aim: To assess the utility of MRI and PET/CT to differentiate benign versus malignant peripheral nerve sheath tumors (MPNST). Methods: We retrospectively identified 68 patients with histologically confirmed tumors. All these had pretreatment magnetic resonance imaging (MRI) studies 17 18-fluorodeoxyglucose positron emission tomography (PET/CT). Age, history neurofibromatosis, maximum size tumor, MR features, standardized uptake values (SUV) from were obtained. used Wilcoxon-Rank sum...