The Effects of Exercise and Activity-Based Physical Therapy on Bone after Spinal Cord Injury

Sutor, Tommy W.; Kura, Jayachandra R.; Mattingly, Alex J.; Otzel, Dana M.; Yarrow, Joshua F.

doi:10.3390/ijms23020608

Cited by 30 publications

(27 citation statements)

References 141 publications

(319 reference statements)

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“…OPG is produced in response to different stimuli and is responsible for orchestrating bone remodelling in osteoblast cells [50,51]. After the electrical stimulation, we did not observe changes in the mRNA levels, but we believe that it would be convenient in future studies to determine the RANKL values to verify the RANKL/OPG ratio, responsible for bone remodelling.…”

Section: Electrical Stimulation Enhances Proliferation and Differenti...mentioning

confidence: 75%

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DC electrical stimulation enhances proliferation and differentiation on N2a and MC3T3 cell lines

et al. 2022

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Background Electrical stimulation is a novel tool to promote the differentiation and proliferation of precursor cells. In this work we have studied the effects of direct current (DC) electrical stimulation on neuroblastoma (N2a) and osteoblast (MC3T3) cell lines as a model for nervous and bone tissue regeneration, respectively. We have developed the electronics and encapsulation of a proposed stimulation system and designed a setup and protocol to stimulate cell cultures. Methods Cell cultures were subjected to several assays to assess the effects of electrical stimulation on them. N2a cells were analyzed using microscope images and an inmunofluorescence assay, differentiated cells were counted and neurites were measured. MC3T3 cells were subjected to an AlamarBlue assay for viability, ALP activity was measured, and a real time PCR was carried out. Results Our results show that electrically stimulated cells had more tendency to differentiate in both cell lines when compared to non-stimulated cultures, paired with a promotion of neurite growth and polarization in N2a cells and an increase in proliferation in MC3T3 cell line. Conclusions These results prove the effectiveness of electrical stimulation as a tool for tissue engineering and regenerative medicine, both for neural and bone injuries. Bone progenitor cells submitted to electrical stimulation have a higher tendency to differentiate and proliferate, filling the gaps present in injuries. On the other hand, neuronal progenitor cells differentiate, and their neurites can be polarized to follow the electric field applied.

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Section: Electrical Stimulation Enhances Proliferation and Differenti...mentioning

confidence: 75%

“…Lower threshold sensitivities to alignment with the applied EF were observed in N2a at [0. 35,50] mV/mm, as well as the proliferation of neurites in the presence of a constant EF (DC). A similar behavior was observed in myoblasts [30], where these were aligned perpendicular to the applied EF.…”

Section: Introductionmentioning

confidence: 99%

DC electrical stimulation enhances proliferation and differentiation on N2a and MC3T3 cell lines

et al. 2022

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“…Moreover, treadmill exercise transiently increases muscle (33) and bone BF (34) in nonneurologically impaired models. However, it is unknown whether ABPT alters bone perfusion after SCI (26,27) or improves bone recovery in paralyzed limbs (10). For example, two studies that used near-infrared spectroscopy to evaluate bone BF in persons with SCI reported no change in proximal tibia perfusion immediately after exercise in response to facilitated plantar flexor exercise (26) or functional electrical stimulation rowing (27), whereas increased bone BF was present in nonneurologically impaired controls.…”

Section: Discussionmentioning

confidence: 99%

“…Activity-based physical therapy (ABPT) modalities that mobilize and/or reload the paralyzed limbs (e.g., bodyweight-supported treadmill training (BWSTT) or passive limb movements) increase BF in the impaired extremities (6)(7)(8) and may improve muscle recovery (9). Various ABPT regimens have also been promoted as a means to increase BMD after SCI (10), as intermittent loading with high peak strains or high strain rates increases BMD in neurologically intact persons (11). However, well-controlled trials evaluating the influence of ABPT on BMD in persons with SCI have produced inconsistent results, especially when assessing the distal femur and proximal tibia sites that are most prone to fracture in this population (10).…”

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confidence: 99%

Passive Cycle Training Promotes Bone Recovery after Spinal Cord Injury without Altering Resting-State Bone Perfusion

Yarrow

Wnek

Conover

et al. 2022

Medicine &Amp; Science in Sports &Amp; Exercise

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IntroductionSpinal cord injury (SCI) produces diminished bone perfusion and bone loss in the paralyzed limbs. Activity-based physical therapy (ABPT) modalities that mobilize and/or reload the paralyzed limbs (e.g., bodyweight-supported treadmill training (BWSTT) and passive-isokinetic bicycle training) transiently promote lower-extremity blood flow (BF). However, it remains unknown whether ABPT alter resting-state bone BF or improve skeletal integrity after SCI.MethodsFour-month-old male Sprague-Dawley rats received T9 laminectomy alone (SHAM; n = 13) or T9 laminectomy with severe contusion SCI (n = 48). On postsurgery day 7, SCI rats were stratified to undergo 3 wk of no ABPT, quadrupedal (q)BWSTT, or passive-isokinetic hindlimb bicycle training. Both ABPT regimens involved two 20-min bouts per day, performed 5 d·wk−1. We assessed locomotor recovery, bone turnover with serum assays and histomorphometry, distal femur bone microstructure using in vivo microcomputed tomography, and femur and tibia resting-state bone BF after in vivo microsphere infusion.ResultsAll SCI animals displayed immediate hindlimb paralysis. SCI without ABPT exhibited uncoupled bone turnover and progressive cancellous and cortical bone loss. qBWSTT did not prevent these deficits. In comparison, hindlimb bicycle training suppressed surface-level bone resorption indices without suppressing bone formation indices and produced robust cancellous and cortical bone recovery at the distal femur. No bone BF deficits existed 4 wk after SCI, and neither qBWSTT nor bicycle altered resting-state bone perfusion or locomotor recovery. However, proximal tibia BF correlated with several histomorphometry-derived bone formation and resorption indices at this skeletal site across SCI groups.ConclusionsThese data indicate that passive-isokinetic bicycle training reversed cancellous and cortical bone loss after severe SCI through antiresorptive and/or bone anabolic actions, independent of locomotor recovery or changes in resting-state bone perfusion.

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“…Sclerostin is a biomarker of SCI-induced OP, playing an important role in mediating bone loss in response to unloading ( 60 ). Canonical Wnt signaling promoted bone formation by stimulating osteoblast differentiation and osteoblast growth ( 61 ). For example, several proteins involved in Wnt signaling were repressed in the distal femur and proximal tibia after SCI, while the number of osteocytes stained for Sclerostin was increased ( 62 ), which contributed to the occurrence of OP.…”

Section: Discussionmentioning

confidence: 99%

Drug discovery in spinal cord injury-induced osteoporosis: a text mining-based study

Wang¹,

Xu²,

Han³

et al. 2022

Ann Transl Med

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Background Spinal cord injury (SCI) and osteoporosis (OP) are common diseases in spine surgery, and OP could be the complication of SCI. However, SCI-induced OP is a complex pathologic process and drug discovery is limited, which restricts the study in the mechanism and treatment of the disease. This study aims to identify the genes and molecular pathways related to SCI-induced OP through computational tools and public datasets, and to explore drug targeting therapy, ultimately preventing the occurrence of OP after SCI. Methods In this study, common genes related to SCI and OP were obtained by text mining, then which conducted the functional analysis. Protein-protein interaction (PPI) networks were constructed by STRING online and Cytoscape software. Finally, core genes and potential drugs were performed after undergoing drug-gene interaction analysis which also completed functional analysis. Results A total of 371 genes common to ‘SCI’ and ‘OP’ were identified by text mining. After functional analysis, 207 significant genes were screened out. Subsequently, PPI analysis yielded 23 genes targetable by 13 drugs which were the candidate to treat SCI-induced OP. Conclusions Taken together, siltuximab, olokizumab, clazakizumab and BAN2401 were first discovered to become the potential drugs for the treatment of SCI-induced OP. Drug discovery using text mining and pathway analysis is a significant way to investigate the pathomechanism of the disease while exploring existing drugs to treat the disease.

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The Effects of Exercise and Activity-Based Physical Therapy on Bone after Spinal Cord Injury

Cited by 30 publications

References 141 publications

DC electrical stimulation enhances proliferation and differentiation on N2a and MC3T3 cell lines

DC electrical stimulation enhances proliferation and differentiation on N2a and MC3T3 cell lines

Passive Cycle Training Promotes Bone Recovery after Spinal Cord Injury without Altering Resting-State Bone Perfusion

Drug discovery in spinal cord injury-induced osteoporosis: a text mining-based study

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