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Item Cartoon illustrating house fly carrying disease.(Indiana State Board of Health, 1912-02) Weed, R.A.[Text in image] Common house fly; DiseaseItem Sost, independent of the non-coding enhancer ECR5, is required for bone mechanoadaptation(Elsevier, 2016-11) Robling, Alexander G.; Kang, Kyung Shin; Bullock, Whitney A.; Foster, William H.; Murugesh, Deepa; Loots, Gabriela G.; Genetos, Damian C.; Anatomy and Cell Biology, School of MedicineSclerostin (Sost) is a negative regulator of bone formation that acts upon the Wnt signaling pathway. Sost is mechanically regulated at both mRNA and protein level such that loading represses and unloading enhances Sost expression, in osteocytes and in circulation. The non-coding evolutionarily conserved enhancer ECR5 has been previously reported as a transcriptional regulatory element required for modulating Sost expression in osteocytes. Here we explored the mechanisms by which ECR5, or several other putative transcriptional enhancers regulate Sost expression, in response to mechanical stimulation. We found that in vivo ulna loading is equally osteoanabolic in wildtype and Sost-/- mice, although Sost is required for proper distribution of load-induced bone formation to regions of high strain. Using Luciferase reporters carrying the ECR5 non-coding enhancer and heterologous or homologous hSOST promoters, we found that ECR5 is mechanosensitive in vitro and that ECR5-driven Luciferase activity decreases in osteoblasts exposed to oscillatory fluid flow. Yet, ECR5-/- mice showed similar magnitude of load-induced bone formation and similar periosteal distribution of bone formation to high-strain regions compared to wildtype mice. Further, we found that in contrast to Sost-/- mice, which are resistant to disuse-induced bone loss, ECR5-/- mice lose bone upon unloading to a degree similar to wildtype control mice. ECR5 deletion did not abrogate positive effects of unloading on Sost, suggesting that additional transcriptional regulators and regulatory elements contribute to load-induced regulation of Sost.Item Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight(Frontiers Media, 2022-08-15) Zamarioli, Ariane; Adam, Gremah; Maupin, Kevin A.; Childress, Paul J.; Brinker, Alexander; Ximenez, Joao P. B.; Chakraborty, Nabarun; Gautam, Aarti; Hammamieh, Rasha; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineUnloading associated with spaceflight results in bone loss and increased fracture risk. Bone morphogenetic protein 2 (BMP2) is known to enhance bone formation, in part, through molecular pathways associated with mechanical loading; however, the effects of BMP2 during spaceflight remain unclear. Here, we investigated the systemic effects of BMP2 on mice sustaining a femoral fracture followed by housing in spaceflight (International Space Station or ISS) or on Earth. We hypothesized that in spaceflight, the systemic effects of BMP2 on weight-bearing bones would be blunted compared to that observed on Earth. Nine-week-old male mice were divided into four groups: 1) Saline+Earth; 2) BMP+Earth; 3) Saline+ISS; and 4) BMP+ISS (n = 10 mice/group, but only n = 5 mice/group were reserved for micro-computed tomography analyses). All mice underwent femoral defect surgery and were followed for approximately 4 weeks. We found a significant reduction in trabecular separation within the lumbar vertebrae after administering BMP2 at the fracture site of mice housed on Earth. In contrast, BMP2 treatment led to a significant increase in trabecular separation concomitant with a reduction in trabecular number within spaceflown tibiae. Although these and other lines of evidence support our hypothesis, the small sample size associated with rodent spaceflight studies limits interpretations. That said, it appears that a locally applied single dose of BMP2 at the femoral fracture site can have a systemic impact on distant bones, affecting bone quantity in several skeletal sites. Moreover, our results suggest that BMP2 treatment works through a pathway involving mechanical loading in which the best outcomes during its treatment on Earth occurred in the weight-bearing bones and in spaceflight occurred in bones subjected to higher muscle contraction.Item WHALEFALL(2021-05) Leamon, Karri; Nordgulen, Eric; Robinson, Cory; Furqueron, ReaganThe whale fall represents a devastating loss not only symbolically of my father, but also a colossal loss to the ecosystem of our great oceans. As the whale begins to sink it blocks out the sun entirely to the creatures beneath. The whale crashes and the sediment of the ocean floor rises up in an intense cloud, further blocking the sun and obscuring the view of the whale. At the precipice of the death, there is no hope of continuing life for the whale; but new life will form. Once the whale is fully settled on the floor, bioluminescent creatures begin to flock to the remains, something that seems nearly impossible in the dark desolate void of the ocean floor, eventually, bringing back the light and life to the whale.