Effect of microgravity on the biomechanical properties of lumbar and caudal intervertebral discs in mice
Introduction
The intervertebral disc is a viscoelastic structure that integrates with rigid spinal vertebrae to support compressive load and provide flexibility. The disc׳s anatomical composition includes a thick, collagenous annulus fibrosus which functions as a ligament attaching to the circumference of the adjacent vertebral endplates, and by doing so, retains the proteoglycan-rich nucleus pulposus. Nucleus proteoglycans are hydrophilic and osmotically attract water to facilitate the swelling that supports compressive loads.
The human intervertebral disc biomechanically responds to a diurnal cycle of loading and unloading (Adams and Hutton, 1983, Adams et al., 1990, Botsford et al., 1994). When loaded by muscle and gravity forces, the applied stress exceeds the disc swelling pressure and fluid is slowly expelled from the disc. This water is typically re-imbibed once load is reduced during rest. Movement of water is accompanied by changes in disc height, intradiscal pressure (Wilke et al., 1999), and biomechanical properties (Adams et al., 1990). The time-depend change in disc height in response to a compressive stress is well-characterized by a three-parameter solid mathematical model (Burns et al., 1984), or similarly, a fluid transport model based on assumptions of endplate permeability, annulus viscoelasticity, and nuclear swelling (Cassidy et al., 1990).
Exposure to microgravity causes a reduction in disc compressive loading in humans. Associated disc water shifts and atrophy of spine-stabilizing muscles causes loss of spinal curvature and lengthening of the vertebral column to more than double the diurnal values (LeBlanc et al., 2000, Lee et al., 2003, Sayson and Hargens, 2008). Astronauts experience increased episodes of low back pain during spaceflight (Wing et al., 1991) and a heightened incidence of herniated nucleus pulposus (HNP) upon return to gravity (Johnston and Campbell, 2010). This elevated risk of post-spaceflight disc herniation is significantly greater for the cervical spine (21 times that of the incidence among a control population) than the lumbar spine (2 to 3 times that of controls) (Johnston and Campbell, 2010). An explanation for the increased susceptibility of cervical discs to post-spaceflight HNP may be due to their increased range of motion (ROM) relative to lumbar discs (White and Panjabi, 1990). The deleterious effects of movement, rather than load, may implicate microgravity-triggered injury mechanisms that could form the basis for in-flight and post-spaceflight countermeasures.
Given the experimental constraints associated with spaceflight studies, rodents are a standard mammalian model for assessing the physiologic effects of prolonged microgravity. Likewise, the rodent caudal (tail) disc is commonly used as a model for the human intervertebral disc. However, the extent murine discs experience diurnal fluctuations that may be exacerbated by microgravity has not been investigated. Yet, studies in rats have demonstrated that two weeks in microgravity degrades disc cellularity, and that this degradation is significantly greater than that observed in tail-suspended ground controls. (Pedrini-Mille et al., 1992, Maynard, 1994). Further, these adverse consequences to disc cellularity and biomechanics are measurable after as little as five days (Sinha et al., 2002). However, no studies have compared the effect of microgravity between rodent caudal and lumbar discs. Rodent lumbar and caudal discs differ functionally and some argue the rodent lumbar disc is a better functional representation of the human lumbar disc (Smit, 2002, Elliott and Sarver, 2004).
To assess microgravity׳s relative effects on lumbar and caudal intervertebral discs, we quantified changes in physiological disc height and biomechanical properties of tissues from mice that had returned from 15-day NASA shuttle mission, STS-131, as compared to those of ground-based controls. Since tail discs have a significantly greater ROM as compared to lumbar discs, we hypothesized that microgravity would have a more pronounced detrimental effect among the caudal discs.
Section snippets
Materials and methods
Experimental procedures were approved by the Institutional and Animal Care and Use Committee at the National Aeronautics and Space Administration (NASA) and followed the Guide for the Care and the Use of Laboratory Animals published by the U.S. National Institutes of Health (NIH Publication no. 85-23, revised 1996).
Results
Seven of the eight caudal discs (spaceflight, n=4; control, n=3) and 13 of the 16 lumbar discs (spaceflight, n=7; control, n=6) contributed data toward the results, other specimens were omitted due to error in dissection and mechanical testing. Results comparing creep parameters and physiological disc height (PDH) between ground control and spaceflight discs are found in Table 1.
PDH, compressive strain, and creep parameter D demonstrated were significantly different between control and
Discussion
We used a murine model to test whether microgravity has a deleterious effect on disc biomechanical properties, and whether the effects vary between lumbar and caudal levels. Our results indicate that caudal discs experience diminished biomechanical properties after 15 days of microgravity, while lumbar discs are not significantly affected. Caudal discs crept more and showed significant decreases in PDH and strain dependence of nuclear swelling (D) compared to the corresponding ground controls.
Conflict of interest statement
The authors have no conflicts of interest to disclose regarding the design and work put into the study and writing this manuscript.
Acknowledgments
We would like to thank NASA, United States Grants NNX09AP11G and NNX10AM18G, and the efforts of NASA׳s Biospecimen Sharing Program Team. Specifically, we thank Richard Boyle, Paul Dumars, Vera Vizir, Kenny Vassigh, and Ken Souza from NASA Ames Research Center. Also, we thank the Life Sciences staff at NASA Kennedy Space Center. From the University of California, San Francisco, we thank Britta Berg-Johansen and Ann Ouyang for their help on some of the analyses and David Lari for his contribution
References (25)
- et al.
Apparent diffusion coefficient of intervertebral discs related to matrix composition and integrity
Magn. Reson. Imaging
(2004) - et al.
Analysis of compressive creep behavior of the vertebral unit subjected to a uniform axial loading using exact parametric solution equations of Kelvin-solid models–Part I. Human intervertebral joints
J. Biomech.
(1984) - et al.
Matrix protein gene expression in intervertebral disc cells subjected to altered osmolarity
Biochem. Biophys. Res. Commun.
(2002) - et al.
Cardiovascular adaptations, fluid shifts, and countermeasures related to space flight
Respir. Physiol. Neurobiol.
(2009) - et al.
The compressive creep properties of normal and degenerated murine intervertebral discs
J. Orthop. Res.
(2004) - et al.
Mechanical differences between lumbar and tail discs in the mouse
J. Orthop. Res.
(2005) - et al.
The effect of a 5-day spaceflight on the immature rate spine
Spine J.
(2002) - et al.
Back pain and spinal changes in microgravity
Orthop. Clin. N. Am.
(1991) - et al.
The effect of posture on the fluid content of lumbar intervertebral discs
Spine
(1983) - et al.
Diurnal changes in spinal mechanics and their clinical significance
J. Bone Joint Surg.
(1990)
In vivo diurnal variation in intervertebral disc volume and morphology
Spine
A water transport model for the creep response of the intervertebral disc
J. Mater. Sci.: Mater. Med.
Cited by (37)
Biomechanical changes in the lumbar spine following spaceflight and factors associated with postspaceflight disc herniation
2022, Spine JournalCitation Excerpt :However, because the postflight risk for disc herniation persists for years following return to Earth, other causal factors are implicated [5]. Moreover, previous work from our group suggests that microgravity-induced changes in disc height and hydration are negligible [9–11]. Recent evidence indicates that lumbar paraspinal muscles experience some degree of atrophy following spaceflight [9,11–14], suggesting that muscle atrophy may be an important factor for disc herniation risk among astronauts.
Neurosurgery and spinal adaptations in spaceflight: A literature review
2021, Clinical Neurology and NeurosurgeryCitation Excerpt :Pathophysiological changes similar to degenerative disc disease have been reported, with significant reduction in glycosaminoglycans, increased collagen:proteoglycan ratio, and increased matrix metalloproteinases [10,11]. A murine study generated support for the theory of intervertebral disc degeneration and loss of intervertebral disc height; yet, it remains possible that anatomical differences and lack of diurnal posturing in mice could account for the absence of supraphysiologic intervertebral disc hydration [12]. Some evidence suggests disc changes occur in different phases, with an initial increase in intervertebral disc height followed by loss of height and degeneration [13].
One strike loading organ culture model to investigate the post-traumatic disc degenerative condition
2021, Journal of Orthopaedic TranslationCitation Excerpt :However, after mechanical compression, the disc was cultured under free swelling condition. Free-swelling culture mimics the condition of spines and IVDs under low or microgravity and could possibly affect cell viability by changes in osmotic pressure [47,48]. The current study employed IVD organ cutlure under physiological loading after one strike loading injury, which would be essential to maintain the disc homeostasis and the continuous solute exchange, and better reveal the post-traumatic IVD phenotypic changes in the degenerative process.
A multi-throughput mechanical loading system for mouse intervertebral disc
2020, Journal of the Mechanical Behavior of Biomedical MaterialsDeveloping Bioreactors to Host Joint-Derived Tissues That Require Mechanical Stimulation
2019, Encyclopedia of Tissue Engineering and Regenerative Medicine: Volumes 1-3Developing bioreactors to host joint-derived tissues that require mechanical stimulation
2019, Encyclopedia of Tissue Engineering and Regenerative Medicine