Regulation of hypoxia-inducible factor-1α (HIF-1α) expression by interleukin-1β (IL-1β), insulin-like growth factors I (IGF-I) and II (IGF-II) in human osteoarthritic chondrocytes

Objective: Hypoxia-inducible factor 1 alpha regulates genes related to cellular survival under hypoxia. This factor is present in osteroarthritic chondrocytes, and cytokines, such as interleukin-1 beta, participate in the pathogenesis of osteoarthritis, thereby increasing the activities of proteolytic enzymes, such as matrix metalloproteinases, and accelerating cartilage destruction. We hypothesize that Hypoxia Inducible Factor-1 alpha (HIF-1α) can regulate cytokines (catabolic action) and/or growth factors (anabolic action) in osteoarthritis. The purpose of this study was to investigate the modulation of HIF-1α in human osteoarthritic chondrocytes by interleukin-1 beta (IL-1β) and insulin-like growth factors I (IGF-I) and II (IGF-II) and to determine the involvement of the phosphatidylinositol-3- kinase (PI-3K) pathway in this process. Methods: Human osteroarthritic chondrocytes were stimulated with IL-1β, IGF-I and IGF-II and LY294002, a specific inhibitor of PI-3K. Nuclear protein levels and gene expression were analyzed by western blot and quantitative reverse transcription-polymerase chain reaction analyses, respectively. Results: HIF-1α expression was upregulated by IL-1β at the protein level but not at the gene level. IGF-I treatment resulted in increases in both the protein and mRNA levels of HIF-1α, whereas IGF-II had no effect on its expression. However, all of these stimuli exploited the PI-3K pathway. Conclusion: IL-1β upregulated the levels of HIF-1α protein post-transcriptionally, whereas IGF-I increased HIF-1α at the transcript level. In contrast, IGF-II did not affect the protein or gene expression levels of HIF-1α. Furthermore, all of the tested stimuli exploited the PI-3K pathway to some degree. 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Obesity versus osteoarthritis: beyond the mechanical overload

<p></p><p>Obesity is currently considered a major public health problem in the world, already reaching epidemic characteristics, according to the World Health Organization. Excess weight is the major risk factor associated with various diseases, such as type 2 diabetes mellitus, hypertension, dyslipidemia and osteometabolic diseases, including osteoporosis and osteoarthritis. Osteoarthritis is the most prevalent rheumatic disease and the leading cause of physical disability and reduced quality of life of the population over 65 years. It mainly involves the joints that bear weight - knees and hips. However, along with the cases of obesity, its prevalence is increasing, and even in other joints, such as hands. Thus, it is assumed that the influence of obesity on the development of OA is beyond mechanical overload. The purpose of this review was to correlate the possible mechanisms underlying the genesis and development of these two diseases. Increased fat mass is directly proportional to excessive consumption of saturated fatty acids, responsible for systemic low-grade inflammation condition and insulin and leptin resistance. At high levels, leptin assumes inflammatory characteristics and acts in the articular cartilage, triggering the inflammatory process and changing homeostasis this tissue with consequent degeneration. We conclude that obesity is a risk factor for osteoarthritis and that physical activity and changes in diet composition can reverse the inflammatory and leptin resistance, reducing progression or preventing the onset of osteoarthritis.</p><p></p

Reynolds number effects on low-speed aerodynamics of a hypersonic configuration

Objective To investigate the effects of a specific protocol of undulatory physical resistance training on maximal strength gains in elderly type 2 diabetics. Methods The study included 48 subjects, aged between 60 and 85 years, of both genders. They were divided into two groups: Untrained Diabetic Elderly (n=19) with those who were not subjected to physical training and Trained Diabetic Elderly (n=29), with those who were subjected to undulatory physical resistance training. The participants were evaluated with several types of resistance training’s equipment before and after training protocol, by test of one maximal repetition. The subjects were trained on undulatory resistance three times per week for a period of 16 weeks. The overload used in undulatory resistance training was equivalent to 50% of one maximal repetition and 70% of one maximal repetition, alternating weekly. Statistical analysis revealed significant differences (p<0.05) between pre-test and post-test over a period of 16 weeks. Results The average gains in strength were 43.20% (knee extension), 65.00% (knee flexion), 27.80% (supine sitting machine), 31.00% (rowing sitting), 43.90% (biceps pulley), and 21.10% (triceps pulley). Conclusion Undulatory resistance training used with weekly different overloads was effective to provide significant gains in maximum strength in elderly type 2 diabetic individuals.Objetivo Verificar os efeitos de um protocolo de treinamento físico resistido ondulatório nos ganhos de força máxima em idosos diabéticos do tipo 2. Métodos Participaram do estudo 48 indivíduos, com idade entre 60 e 85 anos, de ambos os gêneros. Eles foram divididos em dois grupos: Idosos Diabéticos Não Treinados (n=19), com aqueles não submetidos ao treinamento físico, e Idosos Diabéticos Treinados (n=29), que foram submetidos ao protocolo de treinamento físico resistido ondulatório. Os idosos foram avaliados em diversos equipamentos de musculação, antes e após o treinamento resistido ondulatório, por meio do teste de uma repetição máxima. Os participantes realizaram o treinamento resistido ondulatório três vezes por semanas, durante um período de 16 semanas. A sobrecarga do programa foi alternada, sendo em 1 semana equivalente a 50% de uma repetição máxima e, na outra semana, a 70% de uma repetição máxima. A análise estatística revelou diferenças significativas (p<0,05) entre os resultados dos testes pré e pós-período de treinamento resistido ondulatório em um período de 16 semanas. Resultados Os ganhos médios de força foram de 43,20% (extensão de joelho), 65,00% (flexão de joelho), 27,80% (supino sentado máquina), 31,00% (remada sentado), 43,90% (bíceps pulley) e 21,10% (tríceps pulley). Conclusão O protocolo de treinamento resistido ondulatório utilizado com sobrecargas semanais diferentes foi eficiente em proporcionar significativos ganhos de força máxima em idosos diabéticos do tipo 2

Comparação do processo de reparo ósseo em tíbias de ratas normais e osteopênicas Bone repair process in normal and osteopenic female rats' tibiae: a comparative study

O objetivo foi comparar a consolidação óssea em tíbias de ratas normais e osteopênicas. 49 ratas albinas fêmeas, linhagem Wistar, peso médio de 160 (&plusmn; 20g) e 100 dias foram distribuídas em 2 grupos: Ooforectomizado (OOF) e Pseudo-ooforectomizado (Grupo controle - SHAM). 30 dias após a ooforectomia e/ou cirurgia simulada, todas foram submetidas à produção de lesão óssea cortical. Foram sacrificadas na 2ª, 4ª, 6ª e 8ª semanas. Os osteoblastos foram contados. O peso aumentou progressivamente, porém as OOF apresentaram maior peso (p<0,05) quando comparadas as SHAM, à época da segunda cirurgia. 15 dias pós-lesão óssea, as OOF apresentaram maior número de osteoblastos (p<0,05) quando comparados as SHAM. 30 dias pós-lesão óssea houve diminuição no número de osteoblastos, porém os valores foram equivalentes entre os dois grupos OOF e SHAM. 45 dias pós-lesão, apesar da diminuição constante de osteoblastos, o grupo OOF permaneceu elevado quando comparado ao grupo controle (p<0,05). Aos 60 dias o grupo SHAM apresentou menos osteoblastos, sugerindo processo avançado de reparo ósseo. Os animais osteopênicos apresentaram resposta inicial acelerada à lesão óssea, possibilitando a equivalência entre os grupos 30 dias pós-lesão. Mas, após este período apresentaram retardo na mineralização do osteóide, sugerindo atraso tardio no processo de reparo ósseo.<br>The purpose was to compare tibial bone union in normal and osteopenic female rats. Forty-nine Wistar albino female rats weighing 160 g (&plusmn;20g) and 100 days were distributed into 2 groups: Oophorectomized (OOF) and Pseudo-oophorectomized (SHAM). Thirty days later, a cortical injury was produced in all the animals. They were sacrificed in the 2nd, 4th, 6th and 8th weeks. Osteoblasts count was performed. Progressive weight increase was observed, but the OOF group was shown to have gained more weight (p&pound;0.05) than the SHAM group, at the time of the second surgery. After 15 days post-injury, the animals in the OOF group presented a higher number of osteoblasts (p&pound;0.05) compared to the SHAM group. Thirty days after injury, the number of osteoblasts was reduced, but both groups showed similar amounts. Forty-five days after injury, despite a constant reduction, the number of osteoblasts in the OOF group remained high when compared to SHAM (p&pound;0.05) group. After 60 days, we found less osteoblasts in the SHAM group, suggesting an advanced bone repair process. The osteopenic animals showed an early accelerated response, which became equivalent between both groups 30 days after injury. However, after that period, they showed a delayed osteoid mineralization, suggesting delayed late bone repair process