ALEXANDER ROBLING

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..These and other recent mechanisms are reviewed to provide a synthesis of recent experimental findings, in the larger context of whole bone adaptation...

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..Furthermore, Sost deletion protects some trabecular compartments, but not cortical compartments, from bone loss induced by high-dose PTH infusion...

..001). We conclude that estrogen signaling through ER-beta suppresses the mechanical loading response on the periosteal surface of long bones...

..mechanical loading, disuse, and PTH, compared with long bones. We speculate that the history of weight bearing imparts long-term cellular memory to the bone cell network that modulates the cellular response to a wide variety of stimuli...

..Identification of the genes that exert their influence on mechanosensitivity could ultimately lead to therapies that enhance bone mass and reduce fracture susceptibility...

..The results demonstrate the importance of recovery periods for (i) restoring mechanosensitivity to bone cells and (ii) maximizing the osteogenic effects of mechanical loading (exercise) regimens...

..Having time off increases bone formation and improves the resistance to fracture...

..The threshold strain is largest distally, where locomotor bone strains are typically higher and smallest proximally where locomotor bone strains are lower...

..The data also suggest that activities involving higher loading rates are more effective for increasing bone formation, even if the duration of the activity is short...

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..Thus, the 8-kb region of the DMP1 gene is a target for mechanotransduction in osteocytes, and its cis-regulatory activity may be correlated to local strain in bone...

..Bone size was not consistently associated with mechano-responsiveness, indicating that the genetic regulation of mechanotransduction is a complex process that involves a number of genes and is sex-specific...

..We conclude that the PTH regulatory region of MMP-13 also contributes to FSS response and that Nmp4/CIZ plays similar but distinct roles in mediating hormone- and FSS-driven induction of MMP-13 in bone cells...

..Collectively, the results might explain why 4T mice have wider femora and ulnae than do B6 control mice and suggest that mouse Chr. 4 contains a genetic locus that modulates the mechanosensitivity of bone tissue...

..Our data suggest that apoptotic bone cells release HMGB1, that within the marrow HMGB1 is a bone resorption signal, and that intramembraneous and endochondral osteoblasts exhibit differential responses to this cytokine...

..In this prospectus we will review HMGB1 activity at the immune-bone interface and propose a role for HMGB1 as an osteocyte alarmin and mediator of normal remodeling and inflammatory bone loss...

..Modest increases in aBMD and BMC can improve biomechanical properties substantially if the new bone formation is localized to the most biomechanically relevant sites, as occurs during load-induced bone formation...

..Collectively, these data demonstrate that Rac1 critically contributes to increased osteoclast function induced by haploinsufficiency of Nf1 and implicate Rac1 as a rational therapeutic target for osteoporosis...

..We investigated whether the osteogenic response to a simulated high-impact exercise program lasting 4 months could be enhanced by dividing the daily protocol into brief sessions of loading, separated by recovery periods...

..A collection of studies from the clinic and laboratory have provided new insights into how bone building effects of exercise can be maximized. From the available data we have calculated an "osteogenic index" for exercises...

..Collectively, our results identify a what we believe to be a novel cellular and biochemical NF1-haploinsufficient phenotype in osteoclasts that has potential implications for the pathogenesis of NF1 bone disease...

..Many of these processes have implications for bone health, disease, and the feasibility of living in weightless environments (e.g., spaceflight)...

..Of the bones tested, the radius was preferred for mechanical testing because of its high aspect ratio, minimal measurement error, and low variability...

..These findings indicate a role for the 5-HTT in the regulation of bone accrual in the growing skeleton and point to a need for further research into the prescription of SSRIs to children and adolescents...

..A drug therapy that suppresses desensitization pathways may provide an effective means to build bone strength...

..After the initial weeks of loading, bone stopped responding so the degree of adaptation was proportional to the initial peak load magnitude...

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..PTH-induced HMGB1 discharge by UMR cells exhibits similar release kinetics as reported for activated macrophages. These data confirm the presence of the HMGB1/RAGE signaling axis in bone...

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..Exercises that reduce desensitization may provide an effective means to build bone strength...

..However, using mice with a null mutation of the COX-2 gene, we found that a functional COX-2 gene is not required for mechanotransduction. This paradoxical finding may have resulted, in part, from mechanically induced COX-1 activity...

..Only the largest load (17N) caused morphological changes in the distal growth plate cartilage. There was no association found between mineralization and type X collagen localization or capillary invasion and VEGF expression...

..Insights into the mechanisms of Lrp5 activity in mechano-responsiveness hold great potential in the public health arena for understanding the bone-building effects of loading on bone mass, fragility, and fracture risk. ..

..Insights into the mechanisms of mechanosensory loss and recovery hold potential in the public health arena for optimizing the positive effects of loading on bone mass, fragility, and fracture risk. ..

..Insights into the mechanisms of Lrp5 activity in mechano-responsiveness hold great potential in the public health arena for understanding the bone-building effects of loading on bone mass, fragility, and fracture risk. ..