Age-related bone loss is a serious public health problem affecting 15 to 20 million people in the United States (1). In the last decade, several studies have investigated the effects of repeated bouts of exercise on bone density. Although this increase in bone density is mediated via hormones and/or cellular metabolites few studies have linked the increase in bone density with changes in these hormones or metabolites. Therefore, the purpose of this study was to determine the effect of a single bout of weight bearing exercise on the growth factors that alter bone metabolism. Seven healthy female subjects (age 23 ± 5 yrs.) agreed to participate in this study. A V02 max test was administered to each subject to determine their overall fitness level. A treadmill speed corresponding to 70% of their V02 max was then developed and the subjects ran for 40 minm on the treadmill at that speed. Blood samples were drawn pre and 1, 2, 3, 4, 5, 10, 15, 20, 30, 45, and 60 min post-exercise and assayed for serum growth hormone, calcium, parathyroid hormone, and alkaline phosphatase. No significant change was found in parathyroid hormone, calcium, or alkaline phosphatase serum levels. Growth hormone was found to be significantly decreased 30, 45, and 60 min. post-exercise as compared to pre-exercise levels (7.089, 5.399, 4.728, and 11.28 ng/mL, respectively). While this indicates that exercise may cause a depression in growth hormone levels during recovery, the elevated pre-exercise levels of three of the seven subjects masked the exercise stimulated release of growth hormone. Growth hormone stimulates bone absorption via insulin-like growth factors and the GH data suggests that these hormones may have been released well after our last measurement time point. In conchusion, 40 minutes of running exercise at 70% of V02 max does not produce a change in any of the hormones or metabolic factors directly associated with calcium turnover in the bone, suggesting that acute exercise has no immediate effect on bone metabolism. However, the exercise protocol did stimulate GH release which influences bone growth indirectly by its ability to regulate IGF release. Therefore, even though no acute effects were evident, a single bout of exercise may alter the long term control of bone metabolism. / School of Physical Education

[Truncated abstract] Bone remodeling is intricately regulated by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. The elevation in osteoclast number and/or activity is a major hallmark of several common pathological bone disorders including post-menopausal osteoporosis, osteoarthritis, Paget's disease, and tumour-mediated osteolysis. Receptor activator of nuclear factor kappa B ligand (RANKL) is a key cytokine for osteoclast differentiation and activation. The association of RANKL to its cognate receptor, RANK, which is expressed on osteoclast precursors and mature osteoclasts, is essential for osteoclast formation and activation. The intimate interaction between RANKL and RANK triggers the activation of a cascade of signal transduction pathways including NF-κB, NFAT, MAPK and PI3 kinase. Although osteoclast signaling pathways have been intensively studied, the precise molecules and signaling events which underlie osteoclast differentiation and function remain unclear. In order to dissect the molecular mechanism(s) regulating osteoclast differentiation and activity, this thesis herein explores the key RANKL/RANK-mediated signaling pathways. Four truncation mutants within the TNF-like domain of RANKL [(aa160-302), (aa160-268), (aa239-318) and (aa246-318)] were generated to investigate their potential binding to RANK and the activation to RANK-signal transduction pathways. All were found to differentially impair osteoclastogenesis and bone resorption as compared to the wild-type RANKL. The impaired function of the truncation mutants of RANKL on osteoclast formation and function correlates with their reduced ability to activate crucial RANK signaling including NF-κB, IκBα, ERK and JNK. Further analysis revealed that the truncation mutants of RANKL exhibited differentially affinity to RANK as observed by in vitro pull-down assays. ... It is possible that Bryostatin 1 acts via upregulation of a fusion mechanism as the RANKL-induced OCLs are morphologically enlarged, exhibiting increased nuclei number expressing high level of DC-Stamp. Furthermore, Rottlerin was shown to inhibit NF-κB activity, whereas Bryostatin 1 showed the opposing effects. Both inhibitor and activator were also found to modulate other key osteoclastic signaling pathways including NFAT and total c-SRC. These findings implicate, for the first time, Protein Kinase C delta signaling pathways in the modulation of RANKL-induced osteoclast differentiation and activity. Taken together, the studies presented in this thesis provide compelling molecular, biochemical and morphological evidence to suggest that: (1) RANKL mutants might potentially serve as peptide mimic to inhibit RANKL-induced signaling, osteoclastogenesis and bone resorption. (2) A cross talk mechanism between extracellular Ca2+ and RANKL exist to regulate on osteoclast survival. (3) TPA suppressed RANKL-induced osteoclastogenesis predominantly during the early stage of osteoclast differentiation via modulation of NF-κB. (4) Selective inhibition of Protein Kinase C signaling pathways involved in osteoclastogenesis might be a potential treatment method for osteoclast-related bone diseases. (5) Protein Kinase C delta signaling pathways play a key role in regulating osteoclast formation and function.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala univeritet, 2008. / Härtill 5 uppsatser.

Thesis (M.S.)--University of Michigan, 1948.

Thesis (Ph. D.)--Rutgers University, 2007. / "Graduate Program in Ceramic and Materials Science and Engineering." Includes bibliographical references.

Thesis (M.S.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed Oct. 30, 2007). Includes bibliographical references (p. 45-56).

Bibliography: leaves 107-138.

Resumo: A obesidade é uma doença crônica e de caráter epidemiológico, repercutindo de maneira importante na saúde do indivíduo e na sociedade. Atualmente, a cirurgia bariátrica, em especial a Bypass gástrico em Y de Roux (BGYR), vem se popularizando como uma forma de tratamento dessa condição, garantindo perda do excesso de peso superior às terapias convencionais, com manutenção em longo prazo. Contudo, observa-se que, por se tratar de uma cirurgia com componentes restritivos e disabsortivos, o BGYR, pode levar a redução na absorção e ingestão de nutrientes essenciais a homeostase corporal e em especial, a homeostase óssea. Com isso, podem ocorrer alterações no metabolismo ósseo e, consequentemente na estrutura óssea. Os objetivos do presente estudo foram avaliar o efeito da referida cirurgia sobre a ingestão de nutrientes e parâmetros relacionados à remodelação óssea de pacientes obesas antes e após três e seis meses do procedimento, averiguando se existe associação entre a ingestão alimentar e a evolução destes parâmetros. Neste estudo, prospectivo e observacional, foram estudadas 25 mulheres, submetidas ao procedimento de BGYR, no período de maio de 2009 a maio de 2010, no Hospital das Clínicas da Faculdade de Medicina de Botucatu, Unesp. Para avaliação da ingestão energética e de cálcio, magnésio, fósforo, vitamina D e macronutrientes, foi aplicado um registro alimentar de 72 horas, nos três momentos de avaliação, calculando-se as variáveis por meio do software de nutrição Dietpro 5.i Profissional. Os dados comportamentais foram coletados por meio de um protocolo de avaliação, desenvolvido pela equipe, considerando-se uso de tabaco, álcool e prática de atividade física. Foi realizada avaliação antropométrica, aferindo-se circunferências da cintura, abdominal e quadril, além do peso corporal e seus componentes, analisados pelo método... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Obesity is a chronic disease and an epidemic, resulting in a significant way in the health of the individual and society. Nowadays, bariatric surgery in special gastric bypass Roux-Y (BGYR) has become popular as a treatment, ensuring loss of overweight superior to conventional therapies, with long term maintenance. However, it was observed that, because it is a surgery with disabsorptive and restrictive components, the RYGB may lead to reduced absorption and intake of essential nutrients, necessary for the body homeostasis and, specially, bone homeostasis. Thus, changes in bone metabolism may occur and, consequently, changes in bone structure. The objectives of the present study were to evaluate the effect of the surgery on nutrients intake and on parameters related to bone remodeling in obese patients, before and after three and six months of the procedure, by examining the association between food intake and evolution of these parameters. A prospective and observational study evaluated 25 women who underwent the RYGB procedure, from May 2009 to May 2010, at the Hospital of the Medical School of Botucatu, UNESP. For evaluation of energy, calcium, magnesium, phosphorus, vitamin D and macronutrients consumption, a 3 days food record was carried out before and after surgery, and calculated on DietPro 5.i Professional nutrition software. Behavioral data were collected by an assessment protocol, developed by the team, considering use of tobacco, alcohol and physical activity. Anthropometric assessment was performed by measuring waist circumference, waist, hip and body weight, and components of body weight were analyzed by bioelectrical impedance method. Laboratory tests of bone metabolism were also conducted, such as: calcium (urine and serum), serum magnesium and phosphorus, total alkaline phosphatase and bone specific alkaline phosphate (BSAP), parathyroid hormone (PTH), carboxy-te... (Complete abstract click electronic access below) / Orientador: Gláucia M. F. Mazeto / Coorientador: Adriana Mendes / Coorientador: Celso Vieira Leite / Banca: Célia Regina Nogueira / Banca: José Gilberto Henriques Vieira / Mestre