Animal model of simulated microgravity: a comparative study of hindlimb unloading via tail versus pelvic suspension

Chowdhury, Parimal; Long, Ashley; Harris, Gabrielle; Soulsby, Michael; Dobretsov, Maxim

doi:10.1002/phy2.12

Cited by 42 publications

(39 citation statements)

References 55 publications

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“…7b-e), consistent with the kinetics of postnatal weight bearing. To further determine if PIEZO1 mediates skeletal mechanical loading, tail suspension experiments were performed to remove body weight-induced mechanical loading from hind limbs, mimicking the bone loss due to microgravity or disuse 24,25 . As expected, tail suspension induced bone loss in the distal femurs of WT mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk

Wang¹,

You²,

Lotinun³

et al. 2020

Nat Commun

316

314

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Wolff's law and the Utah Paradigm of skeletal physiology state that bone architecture adapts to mechanical loads. These models predict the existence of a mechanostat that links strain induced by mechanical forces to skeletal remodeling. However, how the mechanostat influences bone remodeling remains elusive. Here, we find that Piezo1 deficiency in osteoblastic cells leads to loss of bone mass and spontaneous fractures with increased bone resorption. Furthermore, Piezo1-deficient mice are resistant to further bone loss and bone resorption induced by hind limb unloading, demonstrating that PIEZO1 can affect osteoblastosteoclast crosstalk in response to mechanical forces. At the mechanistic level, in response to mechanical loads, PIEZO1 in osteoblastic cells controls the YAP-dependent expression of type II and IX collagens. In turn, these collagen isoforms regulate osteoclast differentiation. Taken together, our data identify PIEZO1 as the major skeletal mechanosensor that tunes bone homeostasis.

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Section: Resultsmentioning

confidence: 99%

“…Tail suspension model. Tail suspension experiments to remove the body weight induced mechanical loading from hind limbs, mimicked the bone loss due to microgravity or disuse 24,25 . Six-week-old male mice were randomly divided into two groups for tail suspension and ground control.…”

Section: Methodsmentioning

confidence: 99%

Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk

Wang¹,

You²,

Lotinun³

et al. 2020

Nat Commun

316

314

View full text Add to dashboard Cite

show abstract

“…To avoid these issues and to help keep the rats horizontal and presumably more comfortable, we incorporated a pelvic harness (Fig. 1B) similar to that developed by Chowdhury et al (2). We inserted a 10-G insulated solid copper wire (Grainger, Lake Forest, IL) into a medical silicone sheath (Versilon, Saint-Gobain Ceramics & Plastics, Northboro, MA) and bent the coated wire into a double-L shape (Fig.…”

Section: Cage and Hardware Designmentioning

confidence: 99%

A novel partial gravity ground-based analog for rats via quadrupedal unloading

Mortreux

Nagy

et al. 2018

Journal of Applied Physiology

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Musculoskeletal deconditioning is a well-known consequence of microgravity. However, the effects of partial gravity, such as that experienced on the moon (0.16 g) or Mars (0.38 g), on musculoskeletal health remain relatively unexplored. Because Mars is being increasingly viewed as the likely next extraterrestrial site for human exploration, there is an increasing need for Earth-based models that can replicate the long-term physiological effects of microgravity. These models would also offer the opportunity to explore the potential impact of partial artificial gravity (as would be achieved by centrifugation). In this study, we describe a novel partial gravity model that can be employed in rats over extended periods of time. We demonstrate that 2 wk of partial weight bearing at 20, 40, or 70% of normal loading affects the musculoskeletal health of the animals, as evidenced by decreased trabecular bone density (ranging from -7.5 ± 2.7% at 70% of normal loading to -27.9 ± 2.9% at 20%), hindlimb muscle mass, and impaired muscle function as characterized by grip force. This new model will facilitate studies of the physiological changes occurring in partial gravity and allow for the design of potential countermeasures to mitigate these changes. NEW & NOTEWORTHY This research article describes the first quadrupedal unloading model in rats that is sustainable for investigating the physiological alterations occurring in partial gravity environments, providing a new and adaptable model for ground-based research for future space exploration.

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“…In the rat PWB system, we chose to adapt a pelvic harness to support the hind limbs, in lieu of the traditional tail suspension (described thereafter as HLS) [ 20 ] ( Figure 3 ). This pelvic suspension was first described by others in rats undergoing HU [ 39 ] and has been shown to result in similar alterations regarding body weight, muscle atrophy, bone loss and glucose homeostasis compared to tail-suspended animals, while reducing lordosis and spine curvature. The pelvic harness was extremely well tolerated in all of our studies involving either PWB or HLS, and allowed animals to be maintained in the same environment while reducing the time needed to transition from one mechanical loading level to another [ 20 , 35 , 40 , 41 ].…”

Section: Establishing the Rat Partial Weight-bearing (Pwb) Modelmentioning

confidence: 89%

Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model

Mortreux

Rosa‐Caldwell

2020

Life

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For decades, scientists have relied on animals to understand the risks and consequences of space travel. Animals remain key to study the physiological alterations during spaceflight and provide crucial information about microgravity-induced changes. While spaceflights may appear common, they remain costly and, coupled with limited cargo areas, do not allow for large sample sizes onboard. In 1979, a model of hindlimb unloading (HU) was successfully created to mimic microgravity and has been used extensively since its creation. Four decades later, the first model of mouse partial weight-bearing (PWB) was developed, aiming at mimicking partial gravity environments. Return to the Lunar surface for astronauts is now imminent and prompted the need for an animal model closer to human physiology; hence in 2018, our laboratory created a new model of PWB for adult rats. In this review, we will focus on the rat model of PWB, from its conception to the current state of knowledge. Additionally, we will address how this new model, used in conjunction with HU, will help implement new paradigms allowing scientists to anticipate the physiological alterations and needs of astronauts. Finally, we will discuss the outstanding questions and future perspectives in space research and propose potential solutions using the rat PWB model.

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Animal model of simulated microgravity: a comparative study of hindlimb unloading via tail versus pelvic suspension

Cited by 42 publications

References 55 publications

Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk

Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk

A novel partial gravity ground-based analog for rats via quadrupedal unloading

Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model

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