- Bone Metabolism and Diseases
- Bone health and treatments
- Bone health and osteoporosis research
- Spaceflight effects on biology
- TGF-β signaling in diseases
- Connective tissue disorders research
- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Radiopharmaceutical Chemistry and Applications
- Down syndrome and intellectual disability research
- Chronic Disease Management Strategies
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Autophagy in Disease and Therapy
- Birth, Development, and Health
- Nutrition and Health in Aging
- RNA Research and Splicing
- Salivary Gland Disorders and Functions
- Heat shock proteins research
- Diet and metabolism studies
- Blood disorders and treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- dental development and anomalies
University of Arkansas for Medical Sciences
2013-2024
Central Arkansas Veterans Healthcare System
2023
Orthopaedic Research
2005
Institute of Molecular Biology and Biophysics
2005
Abstract Traditional epitranscriptomics relies on capturing a single RNA modification by antibody or chemical treatment, combined with short-read sequencing to identify its transcriptomic location. This approach is labor-intensive and may introduce experimental artifacts. Direct of native using Oxford Nanopore Technologies (ONT) can allow for directly detecting the base modifications, although these modifications might appear as errors. The percent Error Specific Bases (%ESB) was higher than...
Abstract Bone is a common site of cancer metastasis. Breast, prostate, and lung cancers show predilection to metastasize bone. Recently, we reported that the chemokine interleukin 8 (IL-8) stimulates both human osteoclast formation bone resorption. IL-8 mRNA expression was surveyed in panel breast lines MDA-MET, MDA-MB-231, MDA-MB-435, MCF-7, T47D, ZR-75, adenocarcinoma cell line A549. higher with osteolytic potential vivo. Human increased by MDA-MET or A549 cell-conditioned medium, but not...
Gonadal function plays a major role in bone homeostasis. It is widely held that the skeletal consequences of hypogonadism are solely due to loss sex steroids; however, increases turnover begin during perimenopause before decreases serum estradiol levels. These data and our demonstration inhibins acutely regulate cell differentiation vitro led us test whether inhibin A (InhA) regulates mass vivo. Using transgenic model inducible human InhA expression, increased total body mineral density,...
Abstract The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood; antiresorptive agents, current standard of care, do restore weakened architecture. Herein, we reveal diabetic signature in mice at tissue, cell, transcriptome levels demonstrate that three FDA-approved bone-anabolic agents correct it. Diabetes decreased mineral density (BMD) formation, damaged microarchitecture, increased porosity cortical bone, compromised strength. Teriparatide...
Trisomy 21 affects virtually every organ system and results in the complex clinical presentation of Down syndrome (DS). Patterns differences are now being recognized as patients' age these patterns bring about new opportunities for disease prevention treatment. Low bone mineral density (BMD) has been reported many studies males females with DS yet specific effects trisomy on skeleton remain poorly defined. Therefore we determined phenotype measured turnover markers murine model Ts65Dn. Male...
Disuse has been shown to cause a rapid and dramatic loss of skeletal mass strength in the load-bearing bones young mature animals humans. However, little is known about effects disuse aged mammals. The present study was designed determine whether are maintained with extreme age. Fischer 344/Brown Norway male rats (6 32 mo old) were hindlimb suspended (HS) or housed individually for 2 wk. Trabecular volume microarchitecture proximal tibia significantly decreased by HS only rats. reduced...
Leptin, the product of Lep gene, reports levels adiposity to hypothalamus and other regulatory cells, including pituitary somatotropes, which secrete GH. Leptin deficiency is associated with a decline in somatotrope numbers function, suggesting that leptin may be important their maintenance. This hypothesis was tested new animal model exon 17 receptor (Lepr) protein selectively deleted somatotropes by Cre-loxP technology. Organ genotyping confirmed recombination floxed LepR allele only...
Abstract Chaperone‐mediated autophagy (CMA) is a lysosome‐dependent degradation pathway that eliminates proteins are damaged, partially unfolded, or targeted for selective proteome remodeling. CMA contributes to several cellular processes, including stress response and proteostasis. Age‐associated increase in stressors decrease contribute pathologies associated with aging various tissues. bone homeostasis young mice. An age‐associated reduction was reported osteoblast lineage cells; however,...
The process of osteoclastic bone resorption is complex and regulated at multiple levels. role osteoclast (OCL) fusion motility in are unclear, with the movement OCL on largely unexplored. RANKL a potent stimulator murine osteoclastogenesis, Activin A (ActA) enhances that stimulation whole marrow. ActA treatment does not induce osteoclastogenesis stroma-free marrow macrophage cultures (BMM), but rather inhibits RANKL-induced osteoclastogenesis. We hypothesized differentially regulate via...
ABSTRACT Members of the Leprecan family proteins include enzymes, prolyl 3-hydroxylase 1 (P3h1), P3h2, and P3h3, nonenzymatic proteins, Crtap Sc65. Mutations in CRTAP LEPRE1 (encoding P3H1) have been associated with human disease such as recessive osteogenesis imperfecta; however, function Sc65, which is closely related highly homologous to Crtap, unknown. Sc65 has described a synaptonemal complex protein, nucleolar cytoplasmic adapter protein. In light its high sequence similarity an...
Type 2 diabetes (T2D) is on the rise worldwide and associated with various complications of oral cavity. Using an adult-onset preclinical model, we demonstrated profound periodontal alterations in T2D mice, including inflamed gingiva, disintegrated ligaments (PDL), marked alveolar bone loss, unbalanced remodeling due to decreased formation increased resorption. Notably, observed elevated levels Wnt signaling inhibitor sclerostin mice. Motivated by these findings, investigated whether a...
Given the aging population and increased incidence of fracture in elderly population, need exists for agents that can enhance bone healing, particularly situations delayed healing and/or non-union. Our previous studies demonstrated overexpression gonadal peptide, human inhibin A (hInhA), transgenic mice enhances formation strength via osteoblast activity. We tested hypothesis hInhA also exert anabolic effects a murine model distraction osteogenesis (DO), using both administration normal...
Abstract Sequencing of native RNA and corresponding cDNA was performed using Oxford Nanopore Technology. The % Error Specific Bases (%ESB) higher for than cDNA, which enabled detection ribonucleotide modification sites. Based on %ESB differences the two templates, a bioinformatic tool ELIGOS developed applied to rRNAs E. coli, yeast human cells. captured 91%, 95%, ∼75%, respectively, known variety methylation sites in these rRNAs. Yeast transcriptomes from different growth conditions were...
ABSTRACT Bone is a common site for metastasis in breast cancer patients and associated with series of complications that significantly compromise patient survival, partially due to the advanced stage disease at time detection. Currently, no clinically-approved biomarkers can identify or predict development bone metastasis. We recently identified unique peptide fragment parathyroid hormone-related protein (PTHrP), PTHrP(12-48), as validated serum biomarker correlates predicts presence...
Down syndrome (DS), characterized by trisomy of human chromosome 21, is associated with a variety endocrine disorders as well profound skeletal abnormalities. The low bone mass phenotype in DS defined turnover due to decreased osteoclast and osteoblast activity, decreasing the utility antiresorptive agents people DS. Sclerostin antibody (SclAb) therapeutic candidate currently being evaluated anabolic agent. Scl, product sclerostin gene (SOST), inhibits formation through its inhibition Wnt...
Abstract Chaperone-mediated autophagy (CMA) is a protein degradation pathway that eliminates soluble cytoplasmic proteins are damaged, incorrectly folded, or targeted for selective proteome remodeling. However, the role of CMA in skeletal homeostasis under physiological and pathophysiological conditions unknown. To address homeostasis, we deleted an essential component process, namely Lamp2a, from mouse genome. CRISPR-Cas9-based genome editing led to deletion both Lamp2a Lamp2c, another...
Spaceflight and simulated microgravity often associate with pain prediabetes. Streptozotocin (STZ)-induced moderate insulinopenia rat models of prediabetes result in pressure hyperalgesia. The current study was designed to determine whether or not induced by hind limb suspension (HLS) rats lead hyperalgesia.Adult male were divided into HLS (N = 20) control, non-suspended 16) groups, respectively. Bodyweight pressure-pain withdrawal threshold (PPT) measured at regular 2-5 d intervals for 7...