A Modified Technique of Rat Tail Suspension for Longer Periods of Observation

Falcai, Maurício José; Louzada, Mário Jefferson Quirino; Paula, Francisco José Albuquerque de; Okubo, Rodrigo; Volpon, José Batista

doi:10.3357/asem.3248.2012

Cited by 14 publications

(14 citation statements)

References 7 publications

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“…The hindlimb unloading (HU) model is a well-tolerated method to mimic the cephalic fluid shift and removal of skeletal weight-bearing loads seen in spaceflight 12 . Despite the variability of data among independent studies, this model successfully replicates an osteopenia characterized by decreased bone mineral content, weakened bone resistance, and loss of femoral mass, similar to that observed in spaceflight data 13 14 . Moreover, cell-based studies have also been performed using rotational devices, such as the Rotating Wall Vessel (RWV) or Random Positioning Machine (RPM) systems.…”

supporting

confidence: 59%

“…Animal studies were performed using the HU model, which is considered an effective model of bone loss induced by weightlessness and has been described previously 13 . Briefly, Male Sprague-Dawley (SD) rats at 7w age were individually caged and suspended by the tail using a strip of adhesive surgical tape attached to a chain hanging from a pulley.…”

Section: Methodsmentioning

confidence: 99%

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miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity

Wang

Sun

et al. 2015

Sci Rep

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Recent studies have demonstrated that miRNAs can play important roles in osteoblast differentiation and bone formation. However, the function of miRNAs in bone loss induced by microgravity remains unclear. In this study, we investigated the differentially expressed miRNAs in both the femur tissues of hindlimb unloading rats and primary rat osteoblasts (prOB) exposed to simulated microgravity. Specifically, miR-132-3p was found up-regulated and negatively correlated with osteoblast differentiation. Overexpression of miR-132-3p significantly inhibited prOB differentiation, whereas inhibition of miR-132-3p function yielded an opposite effect. Furthermore, silencing of miR-132-3p expression effectively attenuated the negative effects of simulated microgravity on prOB differentiation. Further experiments confirmed that E1A binding protein p300 (Ep300), a type of histone acetyltransferase important for Runx2 activity and stability, was a direct target of miR-132-3p. Up-regulation of miR-132-3p by simulated microgravity could inhibit osteoblast differentiation in part by decreasing Ep300 protein expression, which, in turn, resulted in suppression of the activity and acetylation of Runx2, a key regulatory factor of osteoblast differentiation. Taken together, our findings are the first to demonstrate that miR-132-3p can inhibit osteoblast differentiation and participate in the regulation of bone loss induced by simulated microgravity, suggesting a potential target for counteracting decreases in bone formation.Numerous studies have shown that mechanical stimulations play an important role in the maintenance of bone homeostasis, skeletal morphology and strength during bone formation and development [1][2][3] . By contrast, skeletal unloading, as observed in space flight astronauts or in patients subjected to prolonged immobility or bed-rest, typically induces severe bone loss 4 . The early studies described similar phenomenon, such as cancellous osteoporosis in weight-bearing bones, decreased bone formation and abnormal bone metabolism after space flight 5,6 . During the spaceflight mission on the Soviet/Russian MIR spacecraft and the International Space Station, crew members experienced a persistently enhanced areal bone mineral density lost at an average monthly rate of 1.06% from the spine and 1.0 to 1.6% from the hip, despite adopting an intense exercise regimen to counteract mechanical unloading 7 . Decreased bone formation in both rat cortical and cancellous bones was also demonstrated by tetracycline labeling before and after space flight [8][9][10][11] . In view of spaceflight tremendous costs, more studies have been performed on the ground. The hindlimb unloading (HU) model is a well-tolerated method to mimic the cephalic fluid shift and removal of skeletal weight-bearing loads seen in spaceflight 12 . Despite the variability of data among independent studies, this model successfully replicates an osteopenia characterized by decreased bone mineral content, weakened bone resistance, and loss of femoral mass, simila...

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supporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity

Wang

Sun

et al. 2015

Sci Rep

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“…In this study, hypoactivity secondary to three weeks of tail suspension effectively impaired bone quality, as shown by reduced bone mass, mechanical weakness, and deterioration of trabecular microarchitecture in suspended rats, when compared to the weight‐matched controls. These findings are in agreement with previous reports in literature, which state that hypoactivity due to hindlimb suspension quickly leads to osteopenia (Falcai et al, ; Shimano and Volpon, ). Our histological and BMD data showed severe trabecular bone loss caused by a relatively short duration of suspension.…”

Section: Discussionsupporting

confidence: 94%

The osteogenic effects of swimming on bone mass, strength, and microarchitecture in rats with unloading-induced bone loss

Volpon

Silva

Falcai

et al. 2015

Microsc. Res. Tech.

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The effect of nonweight-bearing exercise on osteoporotic bones remains controversial and inconclusive. The purpose of this study was to evaluate the effects of swimming on osteoporotic tibias of rats submitted to hindlimb suspension. Initially, 20 Wistar rats were used to confirm a significant bone loss following 21 days of unloading. Thirty rats were then divided into 3 groups and followed during 51 days: CON (nonsuspended rats), S + WB (suspended rats for 21 days and then released for regular weight-bearing) and, S + Swim (suspended rats for 21 days and then released from suspension and submitted to swimming exercise). We observed that swimming exercise was effective at fully recovering the bone deterioration caused by suspension, with significant increments in BMD, bone strength and bone volume. On the other hand, regular weight-bearing failed at fully restoring the bone loss induced by unloading. These results indicate that swimming exercise may be a potential tool to improve bone density, strength, and trabecular volume in tibias with bone loss induced by mechanical unloading in suspended rats. We conclude that this modality of activity could be beneficial in improving bone mass, strength, and architecture in osteoporotic individuals induced by disuse, such as bed rest or those exposed to microgravity, who may not be able to perform weight-bearing exercises.

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“…However, data interpretation and comparison with matched groups have been challenging due to the limited sample sizes and large variety with regard to the time of exposure to microgravity and dietary disparities [24]. Thus, hindlimb suspension has been used in the scientific literature as a valid experimental model to simulate the effects of hypogravity [25]. This approach has the advantage of low financial cost, and it is well suited to methodological standardization.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Prior Exercise on Bone Morphological Microstructure after Immobilization in Mice

Suk¹,

Kim²,

Oh³

et al. 2016

Exerc Sci

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We investigated whether swimming activity associated with a three-week period of hypoactivity could prevent the deleterious effects of disuse on the tibias of tail-suspended rats. Forty Wistar rats were divided into five groups: (HS) permanently hindlimb suspension rats; (HS + Swim) rats submitted to unloading interrupted by swimming exercise; (HS + WB) hindlimb suspension rats with interruption for regular weight bearing for the same length of time as the HS + Swim rats; (Control) control rats that were allowed regular cage activities; and (Control + Swim) control rats that underwent swimming exercise. At the end of the experiment, bone mineral density, bone strength, and trabecular quantification were analyzed. The hindlimb-suspended rats exhibited bone quality loss (significant decrease in BMD, bone strength, and deterioration of trabecular and cortical bone architecture; decrease in BV/TV, TbN, TbTh, ConnD, CtV, and CtTh; and increase in TbSp) when compared to control rats. In contrast, trained rats showed a significant increase of 43% in bone mass, 29% in bone strength, 58% in trabecular thickness, 85% in bone volume, 27% in trabeculae number, and 30% in cortical volume, when compared to the hindlimb-suspended rats. We conclude that swimming activity not only ameliorates but also fully prevents the deleterious effects on bone quality in osteopenic rats.

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A Modified Technique of Rat Tail Suspension for Longer Periods of Observation

Cited by 14 publications

References 7 publications

miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity

miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity

The osteogenic effects of swimming on bone mass, strength, and microarchitecture in rats with unloading-induced bone loss

The Effect of Prior Exercise on Bone Morphological Microstructure after Immobilization in Mice

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