Vitamin D is important for bone development with immunomodulatory effects. This study investigated whether feeding CD-1 and interleukin 10 (IL-10) knockout (KO) dams low (25 IU/kg diet) or high (5,000 IU/kg diet) vitamin D affected bone health of dams as well as their offspring. Offspring were weaned to 1 of the 2 diets and followed to young adulthood. Unlike CD-1 dams, IL-10 KO dams experienced greater femur strength with high vitamin D. CD-1 male offspring had reduced femur neck strength and female offspring had smaller, weaker femurs, and weaker lumbar vertebra 2 (LV2) with high maternal vitamin D. IL-10 KO male offspring had larger femurs and female offspring had stronger femurs when weaned to high vitamin D. Low vitamin D did not adversely impact bone health but the optimal level of dietary vitamin D seems to differ between healthy and inflammatory states.

Made available in DSpace on 2017-07-10T17:48:17Z (GMT). No. of bitstreams: 1 Franciele_Navarini.pdf: 271642 bytes, checksum: 28a7bcd130b21facc8ae729e942c43b9 (MD5) Previous issue date: 2009-05-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Four experiments were conducted to evaluate the effects of different electrolyte balance and crude protein in feed for broiler chickens Cobb male line reared in natural conditions of heat stress. In experiment 1, were used 880 chicks in the period from 1 to 7 days of age with an average weight of 52,00 grams. Being housed 22 chicks per experimental unit, comprising a density of 14.10 chicks.m-2 housed in 40 boxes were distributed in a completely randomized design with 8 treatments, five replications. In experiment 2, were used 800 chicks in the period from 8 to 21 days of age with an average weight of 160,00 grams. Being housed 20 chicks per experimental unit, comprising a density of 12.82 chicks.m-2. In experiment 3, were used 640 chicks in the period from 22 to 35 days of age with an average weight of 640 grams. Being housed 16 chicks per experimental unit, comprising a density of 10.25 chicks.m-2. In experiment 4, were used 480 chicks, with an average weight of 1,700 grams, the period from 36 to 42 days of age. Being housed 12 chicks per experimental unit, comprising a density of 7.69 chicks.m-2. The diets were formulated from corn, soybean meal and maize gluten to meet the nutritional requirements of chicks in all experiments, according to Rostagno et al. (2005), except for crude protein whose levels were calculated, considering the levels recommended reducing 5%, 10% and 15%, and two electrolyte balance (200 and 240 mEq.kg-1) in all experiments. The animals received water and food ad libitum. In all the experiments was evaluated zootechnical performance (average gain of weight, average consumption of feed, feed conversion and final weight), and developing bone (index Sedoor). The environmental conditions of the building were monitored six times a day to help the hygrometer, a black globe thermometer and the readings used to calculate the of Black Globe Temperature and Humidity Index (BGHI). During the experimental period, the values of temperature, relative humidity, temperature and black globe BGHI remained above the zone of thermo neutrality of broilers. For the variables of performance in all experiments, except for experiment 4, the chicks had greater weight gain and final weight with the balance of 240 mEq.kg-1. In all experiments, the chicks that received diets with reduced levels of CP showed lower performance on fed diets without reducing protein, independent of the BE. This result is most evident in the diet with a reduction of 15% CP. With regard to blood tests, as reduced levels of CP in the diet, also decreased the concentration of uric acid in serum (p <0.05). For the electrolyte balance of 200 mEq.kg-1 saw the highest amount of calcium in blood serum. The chicks had lower percentage of total protein in blood stock in the range of 240 mEq.kg-1, the average levels of total protein in blood that range from 2.36 (experiment 4) to 2.92 mg.dL-1 (experiment 2) and below 3.6 mg.dL-1, are considered normal. The concentrations of K +, Cl-(Experiment 4) were not influenced (p> 0.05) by treatments. In relation to the concentration of sodium at 21 days of age (Experiment 2), the reduction of diet crude protein decreased (p <0.05) the concentrations of this mineral in serum. This response, however, was not observed at 42 days of age (Experiment 4). For evaluation of bone development, only the levels of CP protein used in the experiment 3, linearly affect the rate of Seedor femur (P <0.05). The effect of GA on the levels of Seedor index was not significant (P <0.05) for all experiments. For chickens from 22 to 35 days of age, levels of CP in the diet caused a linear effect and decreasing the rate of Seedor femur. Only in experiment 1 the levels of protein PB used linearly influence the rate of Seedor tibia (P <0.05), with linear response decreasing. The reduction in the levels of CP in the diet, results in lower values for the index of Seedor by reducing the length and weight of the femur. In general the reduction of 0%, 5%, 10% and 15% crude protein of diet on the recommended per phase, associated with correction of electrolyte balance, was not beneficial in the environmental conditions studied / Foram conduzidos quatro experimentos com o objetivo de avaliar os efeitos de diferentes balanços eletrolíticos e de teores de proteína bruta da ração para frangos de corte machos da linhagem Cobb criados em condições naturais de estresse calórico. No experimento 1 foram utilizadas 880 aves, no período de 1 a 7 dias de idade, com peso médio de 52 gramas. Sendo alojadas 22 aves por unidade experimental, comportando uma densidade de 14,10 aves.m-2 alojados em 40 boxes, distribuídos em delineamento inteiramente casualizados com 8 tratamentos, cinco repetições. No experimento 2, foram utilizadas 800 aves, no período de 8 a 21 dias de idade, com peso médio de 160 gramas. Sendo alojadas 20 aves por unidade experimental, comportando uma densidade de 12,82 aves.m-2. No experimento 3, foram utilizadas 640 aves, no período de 22 a 35 dias de idade com peso médio de 640 gramas. Sendo alojadas 16 aves por unidade experimental, comportando uma densidade de 10,25 aves.m-2. No experimento 4, foram utilizadas 480 aves, com peso médio de 1700 gramas, no período de 36 a 42 dias de idade. Sendo alojadas 12 aves por unidade experimental, comportando uma densidade de 7,69 aves.m-2. As rações foram formuladas a base de milho, farelo de soja e glútem de milho para atender as exigências nutricionais das aves, em todos os experimentos, segundo Rostagno et al. (2005), exceto para proteína bruta cujos níveis foram calculados, considerando os níveis recomendados reduzindo 5%, 10% e 15%, e dois balanços eletrolítico (200 e 240 mEq.kg-1) em todos os experimentos. Os animais receberam água e ração à vontade. Em todos os experimentos foi avaliado desempenho zootécnico (Ganho Médio de Peso, Consumo Médio de Ração, Peso Final e Conversão Alimentar), parâmetros sanguíneos (ácido úrico, proteína total, cálcio, sódio, potássio, cloro); e desenvolvimento ósseo (índice de Sedoor). As condições ambientais do galpão foram monitoradas seis vezes ao dia com auxilio de um termo higrômetro e um termômetro de globo negro e as leituras usadas para calculo do Índice de Temperatura de Globo Negro e Umidade (ITGU). Durante o período experimental, os valores de temperatura, umidade relativa, temperatura de globo negro e ITGU mantiveram-se acima da zona de termoneutralidade para frango de corte. Para as variáveis de desempenho, em todos os experimentos, exceto para o experimento 4, as aves obtiveram maior ganho de peso e peso final com o balanço de 240 mEq.kg-1. Em todos experimentos, as aves que receberam ração com redução dos níveis de PB apresentaram desempenho inferior em relação às alimentadas com ração sem redução protéica, independente do BE. Este resultado fica mais evidente na ração com redução de 15% de PB. Com relação às análises sanguínea, conforme se diminuía os níveis de PB na dieta, diminuía também a concentração de ácido úrico no soro (p<0,05). Para o balanço eletrolítico de 200 mEq.kg-1 verificou-se o maior valor de cálcio no soro sanguíneo. As aves obtiveram menores percentuais sangüíneos de proteína total com balanço na faixa de 240 mEq.kg-1, Os valores médios dos níveis de proteína total no sangue que variam de 2,36 (experimento 4) a 2,92 mg.dL-1 (experimento 2) e encontram-se abaixo de 3,6 mg.dL-1, considerados normais. As concentrações de K+, Cl- (Experimento 4), não foram influenciadas (p>0,05) pelos tratamentos. Em relação à concentração de sódio aos 21 dias de idade (Experimento 2), a redução da proteína bruta da ração diminuiu (p<0,05) as concentrações deste mineral no soro. Esta resposta, entretanto, não foi observada aos 42 dias de idade (Experimento 4). Para avaliação de desenvolvimento ósseo, somente os níveis de proteína PB utilizados no experimento 3, influenciaram linearmente o índice de Seedor do fêmur (P<0,05). O efeito dos níveis de PB sobre o índice de Seedor não foi significativo (P<0,05) para os demais experimentos. Para frangos de 22 a 35 dias de idade, os níveis de PB na ração provocaram efeito linear e decrescente no índice de Seedor do fêmur. Somente no experimento 1 os níveis de proteína PB utilizados influenciaram linearmente o índice de Seedor da tíbia (P<0,05), com resposta linear decrescente. A redução nos níveis de PB na dieta, implica em menores valores para o índice de Seedor, por diminuir o comprimento e peso do fêmur. De maneira geral a redução de 0%, 5%, 10% e 15% da proteína bruta da ração, em relação ao recomendado por fase, associada à correção do balanço eletrolítico, não se mostrou benéfica nas condições ambientais estudadas

There are approximately 600,000 cases of delayed or aberrant fracture healing in people each year, with a small subset of these fractures experiencing disunion. Dietary phosphate deficiency has been shown to impair oxidative phosphorylation and decrease BMP-2 mediated chondrogenic differentiation during fracture healing. Prior studies using pre-committed chondro-progenitor ATDC5 cell line grown in phosphate deficient media showed that energy consumption was linked to protein production and collagen hydroxylation but inversely related to matrix mineralization. The goal of this study was to further define the relationship between energy consumption and BMP-2 mediated stem cell chondrogenic differentiation and further examine how dietary phosphate, and promotion of collagen hydroxylation via ascorbate availability effected these processes. C3H10T1/2 murine cells, a multi-potential cell line, were expanded in pre-differentiation growth medium (DMEM with 10% FBS and 1% Pen/Strep). Once cells reached 60% confluence (day 0), they were grown in differentiating media (α-MEM with 5% FBS and 1X insulin-transferrin-selenium) containing either 100% (1mM) or 25% (0.25mM) inorganic phosphate (Pi), ± 200ng/mL BMP-2(BMP), and ±0.2 mM L-ascorbic acid (AA). In total, there were 8 groups with varying combinations of these three substances. Intracellular lipid, total DNA, protein, and hydroxyproline (HP) content were examined. Chondrocyte gene expression (Col2a1, Acan, ColXa1) and adipocyte gene expression (Pparg, Plin1, Ucp1) were measured to check for cell lineage commitment and specific differentiation of the C3H10T1/2. All measurements were acquired at day 8. The +BMP differentiation media groups contained significantly less DNA content and more protein content than the –BMP differentiation media groups (both p<0.0001). There was also a significant interaction between phosphate and ascorbic acid treatment (p=0.0296), with 25% Pi +AA groups producing significantly more protein than 100% Pi +AA groups. Hydroxyproline production was not different in 100% Pi or 25% Pi conditions (p=0.2951). AA presence in culture media led to greater HP production than culture media lacking AA (p=0.0035) There was a trend of an interaction between phosphate content and AA availability (p=0.0744). 100% Pi ±AA groups produced significantly different amounts of HP while 25% Pi ±AA groups did not produce significantly different amount of HP. Col2a1, Acan, and ColXa1 expression were all increased in +BMP groups. Ascorbic acid treatment groups expressed significantly more Col2a1and Acan than –AA groups. 100% Pi media led to greater Acan expression over 25% Pi groups (p=0.0009), whereas 25% Pi media trended to lead to greater ColXa1 expression over 100% Pi groups (p=0.0734). Pparg and Plin1 expression were increased in the 25% Pi condition. There were no significant differences in expression of Ucp1. C3H10T1/2 cells were significantly affected by phosphate concentration, BMP-2 treatment, and ascorbic acid supplementation. Phosphate deficiency hindered maturation of early chondrocytes into proliferating chondrocytes while also promoting MSC differentiation into the adipocyte cell lineage. Hypertrophic chondrocyte expression was decreased in phosphate deficient media, which may coincide with increased protein production observed in low phosphate conditions. BMP-2 promoted chondrogenesis which resulted in increased protein production. Whereas, lack of ascorbic acid in cell culture media led to decreased hydroxyproline production.

No description available.

No description available.

25‐hydroxycholecalciferol (25‐OHD3) formed via hepatic hydroxylation from vitamin D, cholecalciferol, represents the precursor of the biologically active vitamin D hormone, 1,25‐dihydroxyvitamin D. Due to a higher absorption rate and the omission of one hydroxylation, dietary supplementation of 25‐OHD3 instead of vitamin D3 is considered to be more efficient as plasma concentrations of 25‐OHD3 are increased more pronounced. The present review summarises studies investigating potential beneficial effects on mineral homeostasis, bone metabolism, health status and performance in sows, piglets and fattening pigs. Results are inconsistent. While most studies could not demonstrate any or only a slight impact of partial or total replacement of vitamin D3 by 25‐OHD3, some experiments indicated that 25‐OHD3 might alter physiological processes when animals are challenged, for example, by a restricted mineral supply.

A infecção pelo HIV compromete o sistema imune causando a destruição das células hospedeiras, em maioria as LT-CD4+. O vírus pode ser transmitido através de relação sexual, transfusão sanguínea, contato com materiais perfurocortantes contaminados, transmissão vertical e aleitamento materno. Como medida profilática para a transmissão vertical é adotada a utilização da Highly Active Antiretroviral Therapy (HAART) a partir da décima quarta semana de gestação, que preconiza a redução da carga viral para níveis indetectável até o momento do parto. No entanto são controversos os efeitos que a HAART pode causar na criança em formação e no período neonatal, bem como o efeito deste tratamento no crescimento e desenvolvimento infantil. Inicialmente, foi realizado busca da literatura, de forma sistematizada, nas bases de dados US National Library of Medicine's – National Intitutes of Health (PubMed), Biblioteca Virtual em Saúde (BVS) que engloba Medical Literature Analysis and Retrieval System Online (MEDLINE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Base de dados de enfermagem (BDENF) e SciELO (Scientific Eletronic Library Online). Foram utilizados os descritores: (1) “children HIV Brazil”, (2) “adolescent HIV Brazil”, (3) "anthropometry HIV Brazil" e (4) "nutritional assessment HIV Brazil", acrescentando-se o filtro “and” para pesquisas avançadas. Foram selecionados, após leitura na íntegra, treze artigos. Esses estudos contribuíram para o embasamento técnico-científico do estudo de coorte retrospectiva que foi realizado com 51 crianças, nascidas a termo, expostas ao vírus HIV porém não-infectadas, atendidas em um serviço de referência especializado em atendimento a pessoas vivendo com HIV/Aids, em Palmas, Tocantins, Brasil. Foram coletados dados das crianças ao nascer e dos atendimentos subsequentes categorizados em três momentos (m0, m1, m2 e m3) e informações maternas. Foram utilizados índices antropométricos (peso-para-idade, peso-para-estatura, índice de massa corporal-para-idade, peso-para-estatura e perímetro cefálico-para-idade) para verificação do estado nutricional e índices de proporcionalidade (perímetro cefálico por perímetro torácico, índice de Roher e peso por perímetro cefálico). Foram utilizados os testes estatísticos de X², t-student, Tukey, Friedman, ANOVA e Kruskall Wallis. Os mostram que independente de ser pela atividade do HIV no hospedeiro ou pelo uso da HAART as crianças vivendo com HIV/Aids podem apresentar alterações no metabolismo ósseo, porém a ingestão adequada e o monitoramento sérico de micronutrientes podem evitar desordens desse tipo. Também há associação da HAART com dislipidemia e lipodistrofia nas populações estudadas. No estudo de coorte foi observado tendência ao risco de sobrepeso ou sobrepeso ao longo do acompanhamento, bem como significância estatística em relação a introdução precoce de alimentos e os valores de CD4 e CD8. Não foram encontrados alterações nos índices de proporcionalidade. A escassez de pesquisas com brasileiros tornou as correlações mais difíceis. Conclui-se que o acompanhamento do estado nutricional de crianças e adolescente pode minimizar alterações clínicas e metabólicas, sendo determinante para a avaliação do risco de progressão da doença e, consequentemente, sucesso do tratamento. / HIV infection compromises the immune system causing destruction of the cells mostly hosted as LT-CD4+. The virus can be transmitted through sexual intercourse, blood transfusion, contact with contaminated puncture materials, vertical transmission and breastfeeding. As a prophylactic measure for a vertical transmission the use of highly active antiretroviral therapy (HAART) is adopted from the fourteenth week of gestation, which advocates a reduction of the viral load to undetectable levels until the moment of delivery. However, there are no problems that can cause HAART, which can not be created in life in training and in the neonatal period, as well as the effect of this treatment on infant growth and development. Initially, a literature search was carried out in a systematized manner in the National Library of Medicine (National Institutes of Health (PubMed), Virtual Health Library (VHL) databases that includes the Medical Literature Analysis and Recovery System Online (MEDLINE ), Latin American and Caribbean Literature in Health Sciences (LILACS), Nursing Database (BDENF) and SciELO (Scientific Electronic Library Online). (1) "HIV HIV Brazil", (2) "HIV adolescent HIV", (3) "HIV anthropometry Brazil" and (4) "HIV Brazil nutritional assessment", adding "e" filter For advanced research. Thirteen articles were selected after reading in their entirety. These studies contributed to the development of a retrospective cohort study of 140 uninfected exposed children attended at a referral service specializing in the care of people living with HIV / AIDS in Palmas, Tocantins, Brazil. Data were collected from children at birth and subsequent visits categorized in three moments (m0, m1, m2 and m3) and maternal information. Anthropometric indexes (weight-for-age, weight-for-height, body-for-age-for-age, weight-for-height and cephalic-for-age) were used to verify nutritional status and proportionality indices cephalic by thoracic perimeter, Roher index and head circumference weight). The statistical tests of X², t-student, Tukey, Friedman and ANOVA and Kruskall Wallis were used. They show that regardless of whether it is HIV activity in the host or by the use of HAART, children living with HIV / AIDS may present changes in bone metabolism, but adequate intake and serum micronutrient monitoring may prevent such disorders. There is also association of HAART with dyslipidemia and lipodystrophy in the populations studied. The cohort study showed a tendency to risk of overweight or overweight during follow-up, as well as statistical significance in relation to the early introduction of food and the values of CD4 and CD8. No changes were found in the proportionality indices. The shortage of research with Brazilians made the correlations more difficult. It is concluded that the monitoring of the nutritional status of children and adolescents can minimize clinical and metabolic changes, being determinant for the evaluation of the risk of disease progression and, consequently, treatment success.

Despite numerous studies have demonstrated an association of type 2 diabetes mellitus (T2DM) and osteoporosis, the underlying mechanism connecting these two conditions remains elusive. Clinically, combined calcium and vitamin D supplement is the commonest osteoporosis therapy; however, recent studies have suggested an increase in cardiovascular risks associated with calcium plus vitamin D supplementation. Therefore, an alternative strategy in treating osteoporosis patients with T2DM is urgently needed. In this study, we hypothesized that combined administration of menaquinone-4 (vitamin K₂, biologically active form of vitamin K) and 1α,25-dihydroxyvitamin D₃ (vitamin D₃, biologically active form of vitamin D) as a novel therapy in treating osteoporosis of T2DM patients. Anabolic effect of vitamin K₂ and vitamin D₃, alone or in combination, was assessed on primary osteoblasts harvested from the iliac crests of C57BL/KsJ lean (db⁺/m⁺) and obese/diabetic (db⁺/db⁺, leptin receptor-deficient) mice. Furthermore, the underlying cellular mechanism was also investigated. Serum undercarboxylated osteocalcin (an indication of vitamin K₂ level) level was higher whereas vitamin D₃ level was lower in db⁺/db⁺ mice, and sections of the iliac crests of db⁺/db⁺ mice illustrated extensive porous structures filled with enlarged adipocytes compared with db⁺/m⁺ mice. Lower levels of bone anabolic markers and bone formation transcription factors (osteocalcin, Runx2, Dlx5, ATF4, type I collagen, OSX, alkaline phosphatase (ALP) activity, p-Smad1/5/8 and p-ERK1/2) were observed in the osteoblasts of db⁺/db⁺ mice. Acute vitamin D₃ (10 nM) application elicited a more sustained and greater magnitude of increase of [Ca²⁺]ᵢ in osteoblasts of db⁺/m⁺ mice when compared with db⁺/db⁺ mice. A significantly higher level of calcium deposits in osteoblasts was observed in db⁺/m⁺ mice when compared to db⁺/db⁺ mice. Co-administration of vitamin K₂ (10 nM) and vitamin D₃ (10 nM) caused an enhancement of calcium deposits in osteoblasts in both strains of mice. Vitamins K₂ and D₃ co-administration time-dependently (7, 14 and 21 days) increased the levels of bone anabolic markers and transcription factors for bone formation, with a greater magnitude of increase observed in osteoblasts of db⁺/db⁺ mice. Suppressed expression of calcium-sensing receptor (CaSR), F-actin, V-ATPase, vitamin D receptor (VDR) and pregnane X receptor (PXR) observed in osteoblasts of db⁺/db⁺ mice were partially reversed by combined vitamins treatment. Moreover, combined vitamins K₂ plus D₃ treatment significantly enhanced migration and the appearance of surface microvilli and ruffles of osteoblasts of db⁺/db⁺ mice. Effects of combined vitamins K₂ plus D₃ treatment observed in osteoblasts of db⁺/db⁺ and db⁺/m⁺ mice were eradicated by warfarin (20 µM, a vitamin K epoxide reductase inhibitor). Thus, our results illustrate that vitamins K₂ plus D₃ supplementation is a novel therapeutic strategy in treating osteoporosis of T2DM patients. / 儘管大量研究已證明第二類型糖尿病和骨質疏鬆症的關聯，連接這兩個病症的基本機制仍然是難以捉摸的。在臨床上，鈣和維生素D的綜合補充劑是最常見的骨質疏鬆症治療，然而最近的研究卻表明服用鈣和維生素D的綜合補充劑會增加患者的心血管風險，因此急切需要尋找可以給予同時患有骨質疏鬆症和第二類型糖尿病患者的替代治療。在本研究中，我們假設甲萘醌-4（維生素K₂，維生素K生物活性形式）和1α，25 - 二羥基維生素D₃（維生素D₃，維生素D的生物活性形式）可以嘗試在同時患有骨質疏鬆症和第二類型糖尿病患者身上作為一種革新的療法。本研究從C57BL/KsJ瘦削/非糖尿病 (db⁺/m⁺) 的小鼠和肥胖/帶有第二類型糖尿病基因 (db⁺/db⁺) 兼有瘦素受體缺陷的小鼠的髂嵴原始成骨細胞上對維生素K₂和維生素D₃單獨或組合使用的合成代謝作用進行了評估。此外，我們也對該成骨細胞的底層機制進行了一系列的研究。 / 在肥胖/帶有第二類型糖尿病基因的小鼠血清內低羧骨鈣素水平（維生素K₂水平的指標）較高而維生素D水平較低，另外，它們的髂嵴的部分與瘦削/非糖尿病的小鼠相比，呈現出比較廣泛的多孔結構並填滿了擴大的脂肪細胞。從肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞中，可以觀察到它們的骨合成代謝的標誌物和骨骼形成的轉錄因子 (骨鈣蛋白，Runx2，Dlx5，ATF4，第一類型骨膠原，OSX，鹼性磷酸酶 (ALP) 活性，p-Smad1/5/8和p-ERK1/2) 的水平比較低。急性維生素D₃ (10 nM) 的應用在瘦削/非糖尿病小鼠的成骨細胞比起在肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞引起更持續和更大幅度的細胞內鈣變化增加。在瘦削/非糖尿病小鼠的成骨細胞中比起在肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞有顯著較高的鈣沉積形成。維生素K₂ (10 nM) 和維生素D₃ (10 nM) 的綜合藥在兩種小鼠的成骨細胞中可以有效地增強鈣沉積的形成。維生素K₂和維生素D₃的綜合藥對增加骨合成代謝的標誌物和骨形成轉錄因子的水平有時間依賴性 (7，14和21日)，療程越長至21日，在肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞中有更大的幅度的增加。合併維生素治療能部分有效地逆轉在肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞中被抑制表達的鈣敏感受體 (CASR)，F-肌動蛋白，V-ATP酶，維生素D受體 (VDR) 和孕烷X受體 (PXR)。此外，結合維生素K₂加維生素D₃治療顯著增強了肥胖/帶有第二類型糖尿病基因小鼠的成骨細胞的細胞遷移和增加了成骨細胞表面外觀的微絨毛和褶皺。在瘦削/非糖尿病小鼠的成骨細胞及肥胖/帶有第二類型糖尿病基因的小鼠的成骨細胞上結合維生素K₂加維生素D₃的治療效果被華法林 (20 μM，維生素K環氧化物還原酶抑製劑) 根除。因此，我們的結果証明了維生素K₂加維生素D₃補充劑的結合使用可有效地作為治療第二類型糖尿病患者並患有骨質疏鬆症的一種新的治療策略。 / Poon, Chui Wa Christina. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014.n5203 / Includes bibliographical references (leaves 135-151). / Abstracts also in Chinese. / Title from PDF title page (viewed on 26, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural spine deformity with lateral curve and vertebral rotation occurring predominantly in adolescent girls during the peri-pubertal period. The prevalence of AIS is nearly 4% in Hong Kong and 2-3% worldwide. AIS without treatment or with improper treatment may deteriorate progressively and lead to significant cosmetic problems and functional disabilities. In severe cases, increased mortality rate can result from the associated early onset of cardiopulmonary failure. Up to now, the treatment of the AIS is basically passive through bracing and corrective spinal surgery. The current protocol of treatment is not totally satisfactory since the curve may continue to progress with brace treatment and corrective surgery is associated with major surgery and permanent fusion of parts of the spine. This is due to the fact that one is still uncertain about the etiology of AIS and therefore cannot directly treat the AIS. Among the different proposed etiology of AIS, the role of abnormal skeletal growth and development during peri-pubertal period has been one of the main focuses in addition to genetic predisposition in the development of AIS. / It has been well established that girls with idiopathic scoliosis have a tendency to be taller and more slender than their peers. Recently, it has been shown that the trabecular bone mineral density at the spine, hip, and peripheral bones of AIS girls was lower than their healthy peers. Studies from our center have also demonstrated growth discrepancy between anterior and posterior vertebral column using magnetic resonance imaging (MRI) technique. The vertebral bodies were shown to be slender in AIS patients than that in normal controls. The observation pointed to a disproportionate growth of the anterior and posterior spinal column resulting from imbalance in endochondral and membranous ossification. The present study hypothesizes that the abnormality of skeletal growth could be a systemic problem affected by both endochondral ossification and membranous ossification. The degree of abnormal growth could vary with different curve severities. The concurrent finding of abnormal skeletal growth and osteopenia could be related to certain underlying abnormal genetic factors affecting the etiopathogenesis of AIS. The hypothesis leads to the following objectives: (1) To study the anthropometric measurements and the related changes in AIS girls with different curve severity; (2) To document the presence of abnormal systemic growth through endochondral ossification; (3) To document the presence of abnormal membranous ossification through studies of the morphology and bone mineral density of the midshaft of the appendicular skeleton and the skull; (4) To study the association of occurrence of AIS and its related phenotypes with the genes associated with growth and osteopenia. (Abstract shortened by UMI.) / by Yeung Hiu-Yan. / "January 2006." / Adviser: Jack C. Y. Cheng. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6301. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 206-227). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Activation of tissue-specific genes is a tightly controlled process that normally involves the combined action of several transcription factors and transcriptional co-regulators. The bone-specific osteoca1cin gene (OC) has been used as a prototype to study both tissue-specific and hormonal responsiveness. In this study we have examined the role of Runx2, VDR and C/EBP factors in the regulation of OC gene transcription. Contributions of the Runx and VDRE motifs to OC promoter activity were addressed by introducing point mutations within the context of the rat (-1.1 kb) osteocalcin promoter fused to a CAT-reporter gene. The functional significance of these mutations was assayed following transient transfection and after genomic integration in ROS 17/2.8 osteoblastic cell lines. Furthermore, we tested the effect of these mutations on the chromatin organization of the OC promoter. Our data show that all three Runx sites are required for maximal activation of the OC promoter and that the distal sites contribute significantly to the basal activity. Strikingly, mutation of the three Runx sites abrogates responsiveness of the OC promoter to vitamin D; this loss is also observed when only the Runx sites flanking the VDRE are mutated. Chromatin changes that result in the appearance of DNase I hypersensitive sites during activation of the OC gene are well documented. Mutation of the three Runx sites results in altered chromatin structure as reflected by absence of DNase I hypersensitive sites at the vitamin D response element and over the proximal, tissue-specific basal promoter. These data are consistent with the critical role of Runx2 in osteoblast maturation and bone development. Mutation of the VDRE resulted in a complete loss of vitamin D responsiveness; however, this mutant promoter exhibited increased basal activity. The two DNase I hypersensitive sites characteristic of the transcriptionally active OC gene in osteoblastics cells were not altered upon mutation of the VDRE element, although restriction enzyme accessibility in the proximal promoter region was decreased. We also found an increased level of histone H3 acetylation at the VDRE mutant promoter in comparison to the endogenous gene. Thus binding of VDR to OC promoter is required to achieve a normal transcriptional regulation and chromatin structure of the OC gene. Although Runx2 is considered a master gene for bone development and osteoblast differentiation, it is noteworthy that osteoblast-specific transcription of the rat OC promoter occurs even in the absence of Runx sites. Therefore, other transcription factor(s) should be able to drive OC expression. We characterized a C/EBP enhancer element in the proximal promoter of the rat osteoca1cin gene that resides in close proximity to a Runx element, essential for tissue-specific activation. We find that C/EBPβ or δ and Runx2 factors interact together in a synergistic manner to enhance OC transcription in cell culture systems. Mutational analysis demonstrated that this synergism is mediated through the C/EBP responsive element in the OC promoter and requires a direct interaction between Runx2 and C/EBPβ or δ. Taken together, our findings strongly support a mechanism in which combinatorial interaction of Runx2, VDR, C/EBPβ or δ and probably other transcription factors are needed for regulating OC expression. In this process Runx factors not only act as simple transcriptional trans activators but also by facilitating modifications in promoter architecture and maintaining an active conformation of the target gene promoter.