Effects of long time exposure to simulated micro- and hypergravity on skeletal architecture

Canciani, Barbara; Ruggiu, Alessandra; Giuliani, Alessandra; Panetta, Daniele; Marozzi, Katia; Tripodi, Maria; Salvadori, Piero A.; Cilli, Michele; Ohira, Yoshinobu; Cancedda, Ranieri; Tavella, Sara

doi:10.1016/j.jmbbm.2015.06.014

Cited by 29 publications

(19 citation statements)

References 41 publications

(51 reference statements)

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“…However, it does not seem to be probable that glucocorticoid response to stress is responsible for the changes in muscle and bone induced by hypergravity in mice, since glucocorticoid negatively affects muscle and bone masses (Schakman et al 2009;Tamura et al 2015). Appropriate gravity level is a controversial issue to investigate the effects of hypergravity in muscle and bone (Frey et al 1997;Ikawa et al 2011;Gueguinou et al 2012;Bojados and Jamon 2014;Canciani et al 2015;Gnyubkin et al 2015). Gnyubkin et al (2015) revealed that the effects of chronic hypergravity on bone were dependent on the levels of gravity with a threshold between 2 g (increased bone mass) and 3 g (deleterious for bone).…”

Section: Discussionmentioning

confidence: 99%

The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice

et al. 2016

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Gravity changes concurrently affect muscle and bone as well as induce alterations in vestibular signals. However, the role of vestibular signals in the changes in muscle and bone induced by gravity changes remains unknown. We therefore investigated the effects of vestibular lesions (VL) on the changes in muscle and bone induced by 3 g hypergravity for 4 weeks in C57BL/6J mice. Quantitative computed tomography analysis revealed that hypergravity increased muscle mass surrounding the tibia and trabecular bone mineral content, adjusting for body weight in mice. Hypergravity did not affect cortical bone and fat masses surrounding the tibia. Vestibular lesions blunted the increases in muscle and bone masses induced by hypergravity. Histological analysis showed that hypergravity elevated the cross‐sectional area of myofiber in the soleus muscle. The mRNA levels of myogenic genes such as MyoD, Myf6, and myogenin in the soleus muscle were elevated in mice exposed to hypergravity. Vestibular lesions attenuated myofiber size and the mRNA levels of myogenic differentiation markers enhanced by hypergravity in the soleus muscle. Propranolol, a β‐blocker, antagonized the changes in muscle induced by hypergravity. In conclusion, this study is the first to demonstrate that gravity changes affect muscle and bone through vestibular signals and subsequent sympathetic outflow in mice.

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Section: Discussionmentioning

confidence: 99%

The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice

et al. 2016

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“…Therefore, bone loss is a serious concern for long‐term inhabitants of the space station and for space exploration. Although nutritional supplementation with combination of advanced resistive exercise and bisphosphonates improved the weight bearing BMD the changes are irreversible under microgravity …”

Section: Introductionmentioning

confidence: 99%

“…Although nutritional supplementation with combination of advanced resistive exercise and bisphosphonates improved the weight bearing BMD the changes are irreversible under microgravity. 7,8 Osteoclast (OCL) is hematopoietic origin and differentiation into multinucleated cell (MNC) which resorb bone. 9 The TNF family member, receptor activator for nuclear factor κB ligand (RANKL) is critical for OCL precursor differentiation to form multinucleated OCL in bone microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Microgravity modulation of syncytin‐A expression enhance osteoclast formation

Ethiraj

Link

Sinkway

et al. 2018

J of Cellular Biochemistry

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Microgravity (μXg) experienced by astronauts during space flights causes accelerated bone loss. However, the molecular basis of μXg induced bone loss in space is unclear. Osteoclast (OCL) is the primary bone-resorbing cell. We previously demonstrated that simulated μXg promotes OCL formation. In this study, we identified that μXg induces syncytin-A expression in RAW264.7 preosteoclast cells without RANKL stimulation. We further tested the effect of osteotropic factors such as CXCL5 and 1,25(OH) D to regulate the syncytin-A expression in preosteoclast cells subjected to μXg compared to ground based (Xg) cultures. CXCL5 (25 ng/mL) and 1,25(OH) D (10 ng/mL) increased syncytin-A expression under Xg conditions. However, μXg alone upregulates syncytin-A expression compared to Xg control preosteoclast cells. Confocal microscopy using Lyso-Tracker identified syncytin-A expression co-localized with lysosomes in preosteoclast cells. Acridine orange staining showed RANKL elevated autophagy activity in these cells. Further, siRNA suppression of syncytin-A significantly inhibits autophagy activity in RAW264.7 cells. In addition, knockdown of syncytin-A expression inhibits μXg increased OCL formation in mouse bone marrow cultures. Thus, our findings suggest that targeting syncytin-A expression may be an effective countermeasure to control bone loss under microgravity conditions.

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“…Histomorphometric quantification of new‐formed bone indicates an increase of bone formation with increased implantation time in both scaffolds and also statistically significant differences between the two ceramics at both 1 and 2 month implantation (Figure b). Samples explants at 2 months were also prepared for histology according to a resin embedding technique, which allows the observation of bone deposition dynamics in nondecalcified samples (Canciani et al, ). It was possible to observe time dependent differences in the bone formation process within the two scaffolds (Figure c).…”

Section: Resultsmentioning

confidence: 99%

Beta‐tricalcium phosphate ceramic triggers fast and robust bone formation by human mesenchymal stem cells

Pereira

Benelli

Canciani

et al. 2019

J Tissue Eng Regen Med

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Due to their osteoconductive and inductive properties, a variety of calcium phosphate (CaP) scaffolds are commonly used in orthopaedics as graft material to heal bone defects. In this study, we have used two CaP scaffolds with different hydroxyapatite (HA) and β‐tricalcium phosphate (β‐TCP) ratios (MBCP®; 60/40 and MBCP+®; 20/80) to investigate their intrinsic capacity to favour human bone marrow stem cells (hBMSCs) osteogenic differentiation capacity. We report that MBCP+® showed in in vitro culture model a higher rate of calcium ion release in comparison with MBCP®. In two defined coculture systems, the hBMSC seeded onto MBCP+® presented an increased amount of VEGF secretion, resulting in an enhanced endothelial cell proliferation and capillary formation compared with hBMSC seeded onto MBCP®. When both ceramics combined with hBMSC were implanted in a nude mouse model, we observed a faster osteogenic differentiation and enhancement mature bone deposition sustained by the presence of a vast host vasculature within the MBCP+® ceramics. Bone formation was observed in samples highly positive to the activation of calcium sensing receptor protein (CaSr) on the surface of seeded hBMSC that also shown higher BMP‐2 protein expression. With these data we provide valuable insights in the possible mechanisms of ossification and angiogenesis by hBMSC that we believe to be primed by calcium ions released from CaP scaffolds. Evidences could lead to an optimization of ceramic scaffolds to prime bone repair.

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Effects of long time exposure to simulated micro- and hypergravity on skeletal architecture

Cited by 29 publications

References 41 publications

The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice

The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice

Microgravity modulation of syncytin‐A expression enhance osteoclast formation

Beta‐tricalcium phosphate ceramic triggers fast and robust bone formation by human mesenchymal stem cells

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