Maya Styner

Maya Styner
University of North Carolina at Chapel Hill | UNC · Division of Endocrinology and Metabolism

MD

About

56
Publications
10,149
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1,798
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Introduction
Dr. Maya Styner sees patients and conducts research in the division of Endocrinology and Metabolism at the University of North Carolina at Chapel Hill. Her clinical focus is on general endocrinology with an emphasis on osteoporosis and other disorders of skeletal fragility. Her research centers on the effect of exercise on bone health, including investigation of bone marrow adipose tissue, a poorly understood fat depot.
Additional affiliations
March 2018 - present
University of North Carolina at Chapel Hill
Position
  • Professor (Associate)
July 2012 - February 2018
University of North Carolina at Chapel Hill
Position
  • Professor (Assistant)
July 2010 - June 2012
University of North Carolina at Chapel Hill
Position
  • BIRCWH Scholar/ junior faculty
Education
August 1998 - May 2002

Publications

Publications (56)
Article
Mesenchymal stem cells (MSCs) respond to environmental forces with both cytoskeletal re-structuring and activation of protein chaperones of mechanical information, β-catenin, and yes-associated protein 1 (YAP1). To function, MSCs must differentiate between dynamic forces such as cyclic strains of extracellular matrix due to physical activity and st...
Article
Full-text available
Exercise, typically beneficial for skeletal health, has not yet been studied in lipodystrophy, a condition characterized by paucity of white adipose tissue, with eventual diabetes, and steatosis. We applied a mouse model of global deficiency of Bscl2 (SEIPIN), required for lipid droplet formation. Male twelve-week-old B6 knockouts (KO) and wild typ...
Preprint
Full-text available
Mesenchymal stem cells (MSC) respond to environmental forces with both cytoskeletal re-structuring and activation of protein chaperones of mechanical information, β-catenin and Yes-Associated Protein 1 (YAP1). To function, MSCs must differentiate between dynamic forces such as cyclic strains of extracellular matrix due to physical activity and stat...
Article
Aging induces alterations in bone structure and strength through a multitude of processes, exacerbating common aging- related diseases like osteoporosis and osteoarthritis. Cellular hallmarks of aging are examined, as related to bone and the marrow microenvironment, and ways in which these might contribute to a variety of age-related perturbations...
Article
Full-text available
Context The contribution of lumbar scoliosis to osteoporosis is unknown. Objective To determine prevalence and relationship of lumbar scoliosis to osteoporosis in aging women. Design A cross-sectional analysis used dual-energy X-ray absorptiometry (DXA) scans of randomly selected groups of postmenopausal women (64-68, 74-78, and 84-88 years; N=30...
Article
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Use of the selective estrogen receptor modulator Tamoxifen (TAM) is a mainstay to induce conditional expression of Cre recombinase in transgenic laboratory mice. To excise β-catenin fl/fl in 28-day-old male and female Prrx1-CreER/β-catenin fl/fl mice (C57BL/6), we utilized TAM at 150 mg/kg; despite β-catenin knockout in MSC, we found a significan...
Article
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Purpose of Review To highlight recent basic, translational, and clinical works demonstrating exercise and diet regulation of marrow adipose tissue (MAT) and bone and how this informs current understanding of the relationship between marrow adiposity and musculoskeletal health. Recent Findings Marrow adipocytes accumulate in the bone in the setting...
Article
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Tumor induced osteomalacia (TIO) is a rare cause of impaired bone mineralization mediated by the osteocyte‐derived, phosphaturic hormone: fibroblast growth factor 23 (FGF23). We present the case of a previously healthy 45‐year‐old man who developed fragility fractures at multiple sites (initially metatarsals, eventually ribs, hips, spine, scapula,...
Poster
Full-text available
BACKGROUND: The phosphaturic, bone-derived hormone FGF23, mediates bone loss in TIO. Tumor resection typically results in skeletal healing and reversal of biochemical defects. Case: A 45-year-old Caucasian man with no past medical history presented with non-traumatic fractures of bilateral metatarsals. Over the subsequent 2 years, he sustained frag...
Poster
Full-text available
Introduction: Capable of generating excess catecholamines, untreated extra-adrenal paragangliomas (PGL) result in severe cardiovascular morbidity and mortality. Increasingly, a hereditary basis can be identified to underlie PGLs, though such data is largely absent in non-Caucasian populations. Case 1: A 43 yr. old Kinyarwanda-speaking woman from DR...
Article
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During bone marrow stromal cell (BMSC) differentiation, both Wnt signaling and the development of a rigid cytoskeleton promote commitment to the osteoblastic over adipogenic lineage. β-catenin plays a critical role in the Wnt signaling pathway to facilitate downstream effects on gene expression. We show that β-catenin was additive with cytoskeletal...
Article
Full-text available
Nuclear actin plays a critical role in mediating mesenchymal stem cell (MSC) fate commitment. In marrow derived MSCs, the principal diaphanous-related formin Diaph3 (mDia2) is present in the nucleus and regulates intranuclear actin polymerization, while Diaph1 (mDia1) is localized to the cytoplasm and controls cytoplasmic actin polymerization. We h...
Article
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Marrow adipose tissue (MAT) and its relevance to skeletal health during caloric restriction (CR) is unknown: it remains unclear whether exercise, which is anabolic to bone in a calorie-replete state, alters bone or MAT in CR. We hypothesized that response of bone and MAT to exercise in CR differs from the calorie-replete state. Ten-week-old female...
Article
Full-text available
Osteoporosis, a condition of skeletal decline that undermines quality of life, is treated with pharmacological interventions that are associated with poor adherence and adverse effects. Complicating efforts to improve clinical outcomes, the incidence of obesity is increasing, predisposing the population to a range of musculoskeletal complications a...
Article
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A perimenopausal woman presented with palpitations, hirsutism, and inability to lose weight. Laboratory tests revealed an unusual endocrine hormonal profile including pituitary hormones (TSH, ACTH, prolactin) below reference intervals, and gonadal (testosterone) and adrenal (cortisol) hormones above reference intervals. Ultimately, after a comprehe...
Article
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βcatenin acts as a primary intracellular signal transducer for mechanical and Wnt signaling pathways to control cell function and fate. Regulation of βcatenin in the cytoplasm has been well studied but βcatenin nuclear trafficking and function remains unclear. In a previous study we showed that, in mesenchymal stem cells (MSC), mechanical blockade...
Article
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This case of postgastric bypass osteomalacia, secondary hyperparathyroidism, and resulting pelvic fractures highlights important concepts in bone fragility, as well as the significance of the oft-ordered and poorly understood 25-OH vitamin D. Obesity is well-recognized to be protective against pelvic and hip fractures (1). Although gastric bypass i...
Article
The quantity and quality of bone depends on osteoblastic differentiation of mesenchymal stem cells (MSCs), where adipogenic commitment depletes the available pool for osteogenesis. Cell architecture influences lineage decisions, where interfering with cytoskeletal structure promotes adipogenesis. Mechanical strain suppresses MSC adipogenesis partia...
Article
Full-text available
Marrow mesenchymal stem cells supply bone osteoblasts and adipocytes. Exercise effects to increase bone and decrease fat involve transfer of signals from the cytoplasm into the nucleus to regulate gene expression. We propose that exercise control of stem cell fate relies on structural connections that terminate in the nucleus and involve intranucle...
Article
Full-text available
Actin structure contributes to physiologic events within the nucleus to control mesenchymal stromal cell (MSC) differentiation. Continuous cytochalasin D (Cyto D) disruption of the MSC actin cytoskeleton leads to osteogenic or adipogenic differentiation, both requiring mass transfer of actin into the nucleus. Cyto D remains extranuclear, thus intra...
Article
Full-text available
The relationship between marrow adipose tissue (MAT) and bone health is poorly understood. We used running exercise to ask whether obesity-associated-MAT can be attenuated via exercise and whether this correlates with gains in bone quantity and quality. C57BL/6 mice were divided into diet-induced obesity (DIO n = 14) vs. low-fat diet (LFD n = 14)....
Article
Full-text available
Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT) remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell pool (MSC) that gives rise also to osteoblasts, chondrocytes, and myocytes among other cell types. To date, the presence of MAT has been attributed to preferential bi...
Article
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Muscle Lipid increases with high-fat feeding and diabetes. In trained athletes, increased muscle lipid is not associated with insulin resistance, a phenomenon known as the athlete’s paradox. To understand if exercise altered the phenotype of muscle lipid, female C57BL/6 mice fed CTL or high fat diet (HFD for 6 or 18 wk) were further divided into se...
Article
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Depolymerization of the actin cytoskeleton induces nuclear trafficking of regulatory proteins and global effects on gene transcription. We here show that in mesenchymal stem cells (MSC), cytochalasin D treatment causes rapid cofilin/importin-9 dependent transfer of G-actin into the nucleus. The continued presence of intranuclear actin, which forms...
Article
Full-text available
Studying osteocyte behavior in culture has proven difficult because these embedded cells require spatially coordinated interactions with the matrix and surrounding cells to achieve the osteocyte phenotype. Using an easily attainable source of bone marrow mesenchymal stem cells, we generated cells with the osteocyte phenotype within two weeks. These...
Article
Full-text available
The contribution of marrow adipose tissue (MAT) to skeletal fragility is poorly understood. PPARγ agonists, associated with increased fractures in diabetic patients, increase MAT. Here we asked if exercise could limit the MAT accrual and increase bone formation in the setting of PPARγ agonist treatment. Eight week-old female C57BL/6 mice were treat...
Article
Full-text available
A cell's ability to recognize and adapt to the physical environment is central to its survival and function, but how mechanical cues are perceived and transduced into intracellular signals remains unclear. In mesenchymal stem cells (MSC), high magnitude substrate strain (HMS, ≥2%) effectively suppresses adipogenesis via induction of FAK/mTORC2/Akt...
Poster
Full-text available
Osteocytes modulate bone density through both osteoblast and osteoclast effectors, and " reach out " to interact with cells in the marrow compartment. The stellate morphology and spatial organization of osteocytes are optimal for sensing force and transmitting biochemical signals through their interconnected lacuno-canalicular system. In addition t...
Article
Full-text available
Marrow adipose tissue (MAT), associated with skeletal fragility and hematologic insufficiency, remains poorly understood and difficult to quantify. We tested the response of MAT to high fat diet (HFD) and exercise using a novel volumetric analysis, and compared it to measures of bone quantity. We hypothesized that HFD would increase MAT and diminis...
Article
Full-text available
The cell cytoskeleton interprets and responds to physical cues from the microenvironment. Applying mechanical force to mesenchymal stem cells induces formation of a stiffer cytoskeleton, which biases against adipogenic differentiation and toward osteoblastogenesis. mTORC2, the mTOR complex defined by its binding partner rictor, is implicated in res...
Article
Mechanical strain provides an anti-adipogenic, pro-osteogenic stimulus to mesenchymal stem cells (MSC) through generating intracellular signals and via cytoskeletal restructuring. Recently, mTORC2 has been shown to be a novel mechanical target critical for the anti-adipogenic signal leading to preservation of β-catenin. As mechanical activation of...
Article
Full-text available
Exercise prevents marrow mesenchymal stem cell (MSC) adipogenesis, reversing trends that accompany aging and osteoporosis. Mechanical input, the in-vitro analogue to exercise, limits PPARγ expression and adipogenesis in MSC. We considered whether C/EBPβ might be mechanoresponsive as it is upstream to PPARγ, and also is known to upregulate endoplasm...
Article
Full-text available
Exercise-generated signals are pro-osteogenic and anti-adipogenic within the marrow. In vitro studies indicate that mechanical signals directly block adipogenic differentiation through activation of β-catenin and by limiting PPARγ2 expression. Whether mechanically generated β-catenin can inhibit adipogenesis during PPARγ transactivation is unknown....
Article
Full-text available
The fate of pluripotent mesenchymal stem cells (MSC) is determined through integration of chemical, spatial, and physical signals. The suppression of MSC adipogenesis by mechanical stimuli, which requires Akt-induced inhibition of glycogen synthase kinase 3β (GSK3β) with β-catenin activation, can be enhanced by repetitive dosing within a single day...
Article
Full-text available
Mechanical signals can inactivate GSK3β resulting in stabilization of β-catenin. This signaling cascade is necessary for the inhibition of adipogenesis in mesenchymal stem cells (MSC) that is produced by a daily strain regimen. We considered whether Akt was the mechanically activated kinase responsible for phosphorylation and inactivation of GSK3β...
Article
Full-text available
Mechanical signals can inactivate glycogen synthase kinase 3β (GSK3β), resulting in stabilization of β-catenin. This signaling cascade is necessary for the inhibition of adipogenesis in mesenchymal stem cells (MSC) that is produced by a daily strain regimen. We investigated whether Akt is the mechanically activated kinase responsible for phosphoryl...
Poster
Abstract: Background: Lymphoma tumor cells can secrete excess 1,25-dihydroxyvitamin D, leading to severe hypercalcemia independent of the action of PTH or PTHrp1. Frequently, multiple doses of IV bisphosphonates are required with a risk for adverse effects. Additionally, patients may become refractory to bisphosphonates after repeated administratio...
Article
Full-text available
Mechanical loading induces positive changes in the skeleton due to direct effects on bone cells, which may include regulation of transcription factors that support osteoblast differentiation and function. Flow effects on osteoblast transcription factors have generally been evaluated after short exposures. In this work, we assayed flow effects on os...
Article
Full-text available
Regulation of mesenchymal stem cell (MSC) lineage selection is important for the generation of bone mass. Inhibition of cyclooxygenase-2 (COX2) may increase adipogenesis at the cost of decreasing osteoprogenitor output. Here we investigated the role of COX2 and its products during MSC differentiation. Indomethacin stimulated adipogenesis (increased...
Article
Regulation of skeletal remodeling appears to influence the differentiation of multipotent mesenchymal stem cells (MSC) resident in the bone marrow. As murine marrow cultures are contaminated with hematopoietic cells, they are problematic for studying direct effects of mechanical input. Here we use a modified technique to isolate marrow-derived MSC...
Article
Full-text available
Mechanical stimulation can prevent adipogenic and improve osteogenic lineage allocation of mesenchymal stem cells (MSC), an effect associated with the preservation of β-catenin levels. We asked whether mechanical up-regulation of β-catenin was critical to reduction in adipogenesis as well as other mechanical events inducing alternate MSC lineage se...
Article
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Exposure to fine airborne particulate matter [< or =2.5 microm in aerodynamic diameter (PM(2.5))] has been associated with cardiovascular and hematologic effects, especially in older people with cardiovascular disease. Some epidemiologic studies suggest that adults with diabetes also may be a particularly susceptible population. The purpose of this...
Article
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To investigate ASCA production over time in CD and murine colitis in order to further our understanding of their etiology. Sixty-six CD patients were compared to ulcerative colitis (UC) and irritable bowel syndrome patients with respect to ASCA production as measured by ELISA. ASCA IgG or IgA positivity as well as change in titers over a period of...
Article
To evaluate the use of immunofluorescence asssays for perinuclear antineutrophilic cytoplasmic antibodies (pANCAs) and antibodies to Saccharomyces cerevisiae (ASCAs) in dogs with inflammatory bowel disease (IBD) and assess the clinical value of these serologic markers of the disease. 39 dogs with IBD, 18 dogs with acute diarrhea, 19 dogs with chron...
Article
Alimentary antigens may play a role in the perpetuation of inflammation in Crohn's disease (CD). Yeast antigens are widespread components of food. A proportion of CD patients develop antibodies against the yeast Saccharomyces cerevisiae (ASCA), but little is known about the cellular immune reactivity against food antigens in antibody-positive and -...
Article
Background: Alimentary antigens may play a role in the perpetuation of inflammation in Crohn's disease (CD). Yeast antigens are widespread components of food. A proportion of CD patients develop antibodies against the yeast Saccharomyces cerevisiae (ASCA), but little is known about the cellular immune reactivity against food antigens in antibody-po...
Article
Linomide is a potent immunomodulator that either enhances or suppresses certain immunological processes. Of particular interest is this compound's capacity to inhibit a variety of organ-specific autoimmune diseases. Here, we report on the effects of linomide on several immunological reactions elicited by endotoxin (LPS), both in vivo and in vitro....

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Project (1)
Project
Congenital Generalized Lipodystrophy (CGL) in humans has been associated with increased bone quantity, advanced skeletal age, cystic bone lesions, and increased lean mass. We aim to determine bone quantity and quality in this state of impaired adipogenesis.