Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields.

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using or strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive.

Prevention of age-related neuromuscular junction degeneration in sarcopenia by low-magnitude high-frequency vibration.

Neuromuscular junction (NMJ) degeneration is one of pathological factors of sarcopenia. Low-magnitude high-frequency vibration (LMHFV) was reported effective in alleviating the sarcopenia progress. However, no previous study has investigated treatment effects of LMHFV targeting NMJ degeneration in sarcopenia.

Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial.

Introduction: Sarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective interventions is in need. Previous studies showed that β-hydroxy β-methylbutyrate (HMB) supplement and vibration treatment (VT) enhanced muscle quality, while the coapplication of the two interventions had further improved muscle mass and function in sarcopenic mice model.

Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields.

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using or strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive.

Low-Magnitude Mechanical Signals Combined with Zoledronic Acid Reduce Musculoskeletal Weakness and Adiposity in Estrogen-Deprived Mice.

Unlabelled: Combination treatment of Low-Intensity Vibration (LIV) with zoledronic acid (ZA) was hypothesized to preserve bone mass and muscle strength while reducing adipose tissue accrual associated with complete estrogen (E )-deprivation in young and skeletally mature mice. Complete E -deprivation (surgical-ovariectomy (OVX) and daily injection of aromatase inhibitor (AI) letrozole) were performed on 8-week-old C57BL/6 female mice for 4 weeks following commencement of LIV administration or control (no LIV), for 28 weeks. Additionally, 16-week-old C57BL/6 female E -deprived mice were administered ±LIV twice daily and supplemented with ±ZA (2.

Low-Intensity Vibration Protects the Weight-Bearing Skeleton and Suppresses Fracture Incidence in Boys With Duchenne Muscular Dystrophy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

The ability of low-intensity vibration (LIV) to combat skeletal decline in Duchenne Muscular Dystrophy (DMD) was evaluated in a randomized controlled trial. Twenty DMD boys were enrolled, all ambulant and treated with glucocorticoids (mean age 7.6, height-adjusted -scores [HAZ] of hip bone mineral density [BMD] -2.

G protein-coupled receptor kinase 3 modulates mesenchymal stem cell proliferation and differentiation through sphingosine-1-phosphate receptor regulation.

Background: The bone marrow niche supports hematopoietic cell development through intimate contact with multipotent stromal mesenchymal stem cells; however, the intracellular signaling, function, and regulation of such supportive niche cells are still being defined. Our study was designed to understand how G protein receptor kinase 3 (GRK3) affects bone marrow mesenchymal stem cell function by examining primary cells from GRK3-deficient mice, which we have previously published to have a hypercellular bone marrow and leukocytosis through negative regulation of CXCL12/CXCR4 signaling.

Methods: Murine GRK3-deficient bone marrow mesenchymal stromal cells were harvested and cultured to differentiate into three lineages (adipocyte, chondrocyte, and osteoblast) to confirm multipotency and compared to wild type cells.

The effect of low-intensity whole-body vibration with or without high-intensity resistance and impact training on risk factors for proximal femur fragility fracture in postmenopausal women with low bone mass: study protocol for the VIBMOR randomized controlled trial.

Background: The prevailing medical opinion is that medication is the primary (some might argue, only) effective intervention for osteoporosis. It is nevertheless recognized that osteoporosis medications are not universally effective, tolerated, or acceptable to patients. Mechanical loading, such as vibration and exercise, can also be osteogenic but the degree, relative efficacy, and combined effect is unknown.

Exercise to Mend Aged-tissue Crosstalk in Bone Targeting Osteoporosis & Osteoarthritis.

Aging induces alterations in bone structure and strength through a multitude of processes, exacerbating common aging- related diseases like osteoporosis and osteoarthritis. Cellular hallmarks of aging are examined, as related to bone and the marrow microenvironment, and ways in which these might contribute to a variety of age-related perturbations in osteoblasts, osteocytes, marrow adipocytes, chondrocytes, osteoclasts, and their respective progenitors. Cellular senescence, stem cell exhaustion, mitochondrial dysfunction, epigenetic and intracellular communication changes are central pathways and recognized as associated and potentially causal in aging.

Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity.

Exercise benefits the musculoskeletal system and reduces the effects of cancer. The effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict cancer progression.

Postural Stability in Obese Preoperative Bariatric Patients Using Static and Dynamic Evaluation.

Introduction: Globally, 300 million adults have clinical obesity. Heightened adiposity and inadequate musculature secondary to obesity alter bipedal stance and gait, diminish musculoskeletal tissue quality, and compromise neuromuscular feedback; these physiological changes alter stability and increase injury risk from falls. Studies in the field focus on obese patients across a broad range of body mass indices (BMI >30 kg/m2) but without isolating the most morbidly obese subset (BMI ≥40 kg/m2).

Quantitative ultrasound imaging monitoring progressive disuse osteopenia and mechanical stimulation mitigation in calcaneus region through a 90-day bed rest human study.

Background: Osteoporosis parallels aging and functional mechanical unloading (e.g., space flight and bed rest), jeopardizing mineral density, microstructure, and integrity of bone and leading to an increased risk of fracture.

Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity.

Osteoporosis, a condition of skeletal decline that undermines quality of life, is treated with pharmacological interventions that are associated with poor adherence and adverse effects. Complicating efforts to improve clinical outcomes, the incidence of obesity is increasing, predisposing the population to a range of musculoskeletal complications and metabolic disorders. Pharmacological management of obesity has yet to deliver notable reductions in weight and debilitating complications are rarely avoided.

Marrow Adiposity and Hematopoiesis in Aging and Obesity: Exercise as an Intervention.

Purpose Of Review: Changes in the bone marrow microenvironment, which accompany aging and obesity, including increased marrow adiposity, can compromise hematopoiesis. Here, we review deleterious shifts in molecular, cellular, and tissue activity and consider the potential of exercise to slow degenerative changes associated with aging and obesity.

Recent Findings: While bone marrow hematopoietic stem cells (HSC) are increased in frequency and myeloid-biased with age, the effect of obesity on HSC proliferation and differentiation remains controversial.

Low-intensity vibration increases cartilage thickness in obese mice.

Obesity is associated with an elevated risk of osteoarthritis (OA). We examined here whether high fat diet administered in young mice, compromised the attainment of articular cartilage thickness. Further, we sought to determine if low-intensity vibration (LIV) could protect the retention of articular cartilage in a mouse model of diet-induced obesity.

Mechanical signals protect stem cell lineage selection, preserving the bone and muscle phenotypes in obesity.

The incidence of obesity is rapidly rising, increasing morbidity and mortality rates worldwide. Associated comorbidities include type 2 diabetes, heart disease, fatty liver disease, and cancer. The impact of excess fat on musculoskeletal health is still unclear, although it is associated with increased fracture risk and a decline in muscular function.

The Efficacy of Low-intensity Vibration to Improve Bone Health in Patients with End-stage Renal Disease Is Highly Dependent on Compliance and Muscle Response.

Rational And Objectives: Low intensity vibration (LIV) may represent a nondrug strategy to mitigate bone deficits in patients with end-stage renal disease.

Materials And Methods: Thirty end-stage renal patients on maintenance hemodialysis were randomized to stand for 20 minutes each day on either an active or placebo LIV device. Analysis at baseline and completion of 6-month intervention included magnetic resonance imaging (tibia and fibula stiffness; trabecular thickness, number, separation, bone volume fraction, plate-to-rod ratio; and cortical bone porosity), dual-energy X-ray absorptiometry (hip and spine bone mineral density [BMD]), and peripheral quantitative computed tomography (tibia trabecular and cortical BMD; calf muscle cross-sectional area).

Exercise Decreases Marrow Adipose Tissue Through ß-Oxidation in Obese Running Mice.

The relationship between marrow adipose tissue (MAT) and bone health is poorly understood. We used running exercise to ask whether obesity-associated MAT can be attenuated via exercise and whether this correlates with gains in bone quantity and quality. C57BL/6 mice were divided into diet-induced obesity (DIO, n = 14) versus low-fat diet (LFD, n = 14).

Cell Mechanosensitivity is Enabled by the LINC Nuclear Complex.

Mechanoresponses in mesenchymal stem cells (MSCs) guide both differentiation and function. In this review, we focus on advances in0 our understanding of how the cytoplasmic cytoskeleton, nuclear envelope and nucleoskeleton, which are connected via LINC () complexes, are emerging as an integrated dynamic signaling platform to regulate MSC mechanobiology. This dynamic interconnectivity affects mechanical signaling and transfer of signals into the nucleus.

Low intensity vibration mitigates tumor progression and protects bone quantity and quality in a murine model of myeloma.

Myeloma facilitates destruction of bone and marrow. Since physical activity encourages musculoskeletal preservation we evaluated whether low-intensity vibration (LIV), a means to deliver mechanical signals, could protect bone and marrow during myeloma progression. Immunocompromised-mice (n=25) were injected with human-myeloma cells, while 8 (AC) were saline-injected.

Effect of Low-Magnitude Mechanical Stimuli on Bone Density and Structure in Pediatric Crohn's Disease: A Randomized Placebo-Controlled Trial.

Pediatric Crohn's Disease (CD) is associated with low trabecular bone mineral density (BMD), cortical area, and muscle mass. Low-magnitude mechanical stimulation (LMMS) may be anabolic. We conducted a 12-month randomized double-blind placebo-controlled trial of 10 minutes daily exposure to LMMS (30 Hz frequency, 0.

Associations of Computed Tomography-Based Trunk Muscle Size and Density With Balance and Falls in Older Adults.

Background: Deficits in balance and muscle function are important risk factors for falls in older adults. Aging is associated with significant declines in muscle size and density, but associations of trunk muscle size and density with balance and falls in older adults have not been previously examined.

Methods: Trunk muscle size (cross-sectional area) and attenuation (a measure of tissue density) were measured in computed tomography scans (at the L2 lumbar level) in a cohort of older adults (mean ± SD age of 81.