Ressenyes

Index de les obres ressenyades: Jaime ALVAR ; Carmen BLÁZQUEZ ; Carlos WAGNER (eds.), Héroes, semidioses y daimone

Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis

BACKGROUND: Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated. This has meant that no significant advances in therapeutic strategies have emerged, with joint replacement surgery being the mainstay of treatment. METHODS: In this study we have used an integrated genomics profiling and computational biology based strategy to identify the key osteoblast genes and gene clusters whose expression is altered in response to dexamethasone exposure. Primary human osteoblasts were exposed to dexamethasone in vitro and microarray based transcriptome profiling completed. RESULTS: These studies identified approximately 500 osteoblast genes whose expression was altered. Functional characterization of the transcriptome identified developmental networks as being reactivated with 106 development associated genes found to be differentially regulated. Pathway reconstruction revealed coordinate alteration of members of the WNT signaling pathway, including frizzled-2, frizzled-7, DKK1 and WNT5B, whose differential expression in this setting was confirmed by real time PCR. CONCLUSION: The WNT pathway is a key regulator of skeletogenesis as well as differentiation of bone cells. Reactivation of this pathway may lead to altered osteoblast activity resulting in decreased bone mineral density, the pathological hallmark of osteoporosis. The data herein lend weight to the hypothesis that alterations in developmental pathways drive the initiation and progression of osteoporosis

Phosphate decreases urine calcium and increases calcium balance: A meta-analysis of the osteoporosis acid-ash diet hypothesis

<p>Abstract</p> <p>Background</p> <p>The acid-ash hypothesis posits that increased excretion of "acidic" ions derived from the diet, such as phosphate, contributes to net acidic ion excretion, urine calcium excretion, demineralization of bone, and osteoporosis. The public is advised by various media to follow an alkaline diet to lower their acidic ion intakes. The objectives of this meta-analysis were to quantify the contribution of phosphate to bone loss in healthy adult subjects; specifically, a) to assess the effect of supplemental dietary phosphate on urine calcium, calcium balance, and markers of bone metabolism; and to assess whether these affects are altered by the b) level of calcium intake, c) the degree of protonation of the phosphate.</p> <p>Methods</p> <p>Literature was identified through computerized searches regarding phosphate with surrogate and/or direct markers of bone health, and was assessed for methodological quality. Multiple linear regression analyses, weighted for sample size, were used to combine the study results. Tests of interaction included stratification by calcium intake and degree of protonation of the phosphate supplement.</p> <p>Results</p> <p>Twelve studies including 30 intervention arms manipulated 269 subjects' phosphate intakes. Three studies reported net acid excretion. All of the meta-analyses demonstrated significant decreases in urine calcium excretion in response to phosphate supplements whether the calcium intake was high or low, regardless of the degree of protonation of the phosphate supplement. None of the meta-analyses revealed lower calcium balance in response to increased phosphate intakes, whether the calcium intake was high or low, or the composition of the phosphate supplement.</p> <p>Conclusion</p> <p>All of the findings from this meta-analysis were contrary to the acid ash hypothesis. Higher phosphate intakes were associated with decreased urine calcium and increased calcium retention. This meta-analysis did not find evidence that phosphate intake contributes to demineralization of bone or to bone calcium excretion in the urine. Dietary advice that dairy products, meats, and grains are detrimental to bone health due to "acidic" phosphate content needs reassessment. There is no evidence that higher phosphate intakes are detrimental to bone health.</p

Effects of Fluoride on Rachitic Rats

Both vitamin D-deficient diet and fluoride intake affect calcified tissues and parathyroids in growing rats. Studies were designed to investigate effects of low fluoride intake on rachitic rat femoral bones and parathyroids. Holtzman rats placed on rachitic diet were given distilled water to which 4 , 8, and 20 ppm fluoride a s NaF was added. Control groups consisted of rats on normal laboratory diet and tap water, normal diet and fluoride-treated water, and rachitic diet and tap water. Tetracycline was administered to all groups 5 and 15 days before sacrifice. Animals were provided with these diets and appropriate waters ad libitum until sacrificed after 4 weeks treatment. Parathyroids were removed and prepared for routine paraffin sectioning. Femurs were removed and prepared for routine frozen and paraffin sectioning. Naphthol AS-BI phosphoric acid was used a s substrate for Burstone\u27s method of acid and alkaline phosphatase activity. Bone and parathyroid sections were stained with H & E and PAS. Compared with rachitic control rats , f luoride-treated rachitic rats showed: (1) a slight decrease in body growth rate, and femur weight and length: (2) a slight increase in diaphysial cortical thickness: (3) no change in either phosphatase activity: (4) a decrease in distance between periosteal tetracycline labels: (5) no apparent histological change in parathyroids: and (6) no marked change in size or numbers of femoral diaphysial resorption spaces. These observations indicate that at these dosages, fluoride: (1) caused delayed rate of periosteal bone mineralization measured by tetracycline labels. As the fluoride dosage increased, distances between labels markedly decreased. (2) had no apparent effect on either phosphatase enzyme activity. Activity was seen at periosteal and endosteal surfaces, and in cortical resorption spaces. Activity increased over normal controls, but was similar to those of rachitic controls

Effects of Fluoride on Rachitic Rats

Both vitamin D-deficient diet and fluoride intake affect calcified tissues and parathyroids in growing rats. Studies were designed to investigate effects of low fluoride intake on rachitic rat femoral bones and parathyroids. Holtzman rats placed on rachitic diet were given distilled water to which 4 , 8, and 20 ppm fluoride a s NaF was added. Control groups consisted of rats on normal laboratory diet and tap water, normal diet and fluoride-treated water, and rachitic diet and tap water. Tetracycline was administered to all groups 5 and 15 days before sacrifice. Animals were provided with these diets and appropriate waters ad libitum until sacrificed after 4 weeks treatment. Parathyroids were removed and prepared for routine paraffin sectioning. Femurs were removed and prepared for routine frozen and paraffin sectioning. Naphthol AS-BI phosphoric acid was used a s substrate for Burstone\u27s method of acid and alkaline phosphatase activity. Bone and parathyroid sections were stained with H & E and PAS. Compared with rachitic control rats , f luoride-treated rachitic rats showed: (1) a slight decrease in body growth rate, and femur weight and length: (2) a slight increase in diaphysial cortical thickness: (3) no change in either phosphatase activity: (4) a decrease in distance between periosteal tetracycline labels: (5) no apparent histological change in parathyroids: and (6) no marked change in size or numbers of femoral diaphysial resorption spaces. These observations indicate that at these dosages, fluoride: (1) caused delayed rate of periosteal bone mineralization measured by tetracycline labels. As the fluoride dosage increased, distances between labels markedly decreased. (2) had no apparent effect on either phosphatase enzyme activity. Activity was seen at periosteal and endosteal surfaces, and in cortical resorption spaces. Activity increased over normal controls, but was similar to those of rachitic controls