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Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity

Published on Jun 1, 2019in Nature Reviews Endocrinology24.646
· DOI :10.1038/s41574-019-0170-1
Gabriel M. Pagnotti9
Estimated H-index: 9
(IUPUI: Indiana University – Purdue University Indianapolis),
Maya Styner19
Estimated H-index: 19
(UNC: University of North Carolina at Chapel Hill)
+ 6 AuthorsClinton T. Rubin3
Estimated H-index: 3
(SBU: Stony Brook University)
Abstract
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. By contrast, exercise shows promise as a non-invasive and non-pharmacological method of regulating both osteoporosis and obesity. The principal components of exercise — mechanical signals — promote bone and muscle anabolism while limiting formation and expansion of fat mass. Mechanical regulation of bone and marrow fat might be achieved by regulating functions of differentiated cells in the skeletal tissue while biasing lineage selection of their common progenitors — mesenchymal stem cells. An inverse relationship between adipocyte versus osteoblast fate selection from stem cells is implicated in clinical conditions such as childhood obesity and increased marrow adiposity in type 2 diabetes mellitus, as well as contributing to skeletal frailty. Understanding how exercise-induced mechanical signals can be used to improve bone quality while decreasing fat mass and metabolic dysfunction should lead to new strategies to treat chronic diseases such as osteoporosis and obesity. This Review discusses how signals arising from activity are perceived by cell populations and how the cells respond to them, with particular emphasis on the musculoskeletal and adipose systems. The potential of exercise as a non-invasive and non-pharmacological method of regulating osteoporosis and obesity is also outlined.
  • References (343)
  • Citations (3)
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References343
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#1Gunes Uzer (UNC: University of North Carolina at Chapel Hill)H-Index: 15
#2Guniz Bas (BSU: Boise State University)H-Index: 1
Last. Janet Rubin (UNC: University of North Carolina at Chapel Hill)H-Index: 45
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Abstract βcatenin acts as a primary intracellular signal transducer for mechanical and Wnt signaling pathways to control cell function and fate. Regulation of βcatenin in the cytoplasm has been well studied but βcatenin nuclear trafficking and function remains unclear. In a previous study we showed that, in mesenchymal stem cells (MSC), mechanical blockade of adipogenesis relied on inhibition of βcatenin destruction complex element GSK3β (glycogen synthase kinase 3β) to increase nuclear βcatenin...
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#1Alex HanH-Index: 6
#2Steven L. BokshanH-Index: 6
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By the sixth decade of life, nearly one quarter of the population has substantial muscle atrophy, or sarcopenia. Despite the creation of a standardized definition of sarcopenia by the European Working Group on Sarcopenia in Older People, variability may exist in the diagnostic criteria utilized for clinical sarcopenia research. The primary objectives of this review were to characterize diagnostic criteria used for measurement of sarcopenia in original studies, and to describe associations betwee...
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#1Cheryl L. Cox (St. Jude Children's Research Hospital)H-Index: 22
#2Liang Zhu (University of Texas Health Science Center at Houston)H-Index: 14
Last. Kirsten K. Ness (St. Jude Children's Research Hospital)H-Index: 54
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#2Lina Aires (ETH Zurich)H-Index: 3
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A robust nanopillar platform with increased spatial resolution reveals that perinuclear forces, originating from stress fibres spanning the nucleus of fibroblasts, are significantly higher on these nanostructured substrates than the forces acting on peripheral adhesions. Many perinuclear adhesions embrace several nanopillars at once, pulling them into β1-integrin- and zyxin-rich clusters, which are able to translocate in the direction of cell motion without losing their tensile strength. The hig...
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Purpose of Review Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles ...
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#1Vihitaben S. Patel (SBU: Stony Brook University)H-Index: 3
#2M. Ete Chan (SBU: Stony Brook University)H-Index: 7
Last. Clinton T. Rubin (SBU: Stony Brook University)H-Index: 3
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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.
4 CitationsSource
Optimal osteogenic mechanical loading requires the application of high-magnitude strains at high rates. High-intensity resistance and impact training (HiRIT) applies such loads but is not traditionally recommended for individuals with osteoporosis because of a perceived high risk of fracture. The purpose of the LIFTMOR trial was to determine the efficacy and to monitor adverse events of HiRIT to reduce parameters of risk for fracture in postmenopausal women with low bone mass. Postmenopausal wom...
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Abstract The quantity and quality of bone depends on osteoblastic differentiation of mesenchymal stem cells (MSCs), where adipogenic commitment depletes the available pool for osteogenesis. Cell architecture influences lineage decisions, where interfering with cytoskeletal structure promotes adipogenesis. Mechanical strain suppresses MSC adipogenesis partially through RhoA driven enhancement of cytoskeletal structure. To understand the basis of force-driven RhoA activation, we considered critica...
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#2Serkalem Demissie (BU: Boston University)H-Index: 56
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Older adults with type 2 diabetes (T2D) tend to have normal or greater areal bone mineral density (aBMD), as measured by DXA, than those who do not have diabetes (non-T2D). Yet risk of fracture is higher in T2D, including 40% to 50% increased hip fracture risk. We used HR-pQCT to investigate structural mechanisms underlying skeletal fragility in T2D. We compared cortical and trabecular bone microarchitecture, density, bone area, and strength in T2D and non-T2D. In secondary analyses we evaluated...
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