Mechanisms of bone remodeling during weight-bearing exercise

2006 ◽  
Vol 31 (6) ◽  
pp. 655-660 ◽  
Author(s):  
Ronald Zernicke ◽  
Christopher MacKay ◽  
Caeley Lorincz
Keyword(s):  
Mechanical Loading ◽  
Bone Structure ◽  
Weight Bearing ◽  
Bone Cell ◽  
Bone Adaptation ◽  
Bone Modeling ◽  
Extrinsic Factors ◽  
Paracrine Factors ◽  
Loading Effects ◽  
Exercise Induced

Exercise-induced mechanical loading can have potent effects on skeletal form and health. Both intrinsic and extrinsic factors contribute to bone structure and function. Mechanical simuli (e.g., strain magnitude, frequency, rate, and gradients, as well as fluid flow and shear stress) have potent influences on bone-cell cytoskeleton and associated signalling pathways. Although the immature skeleton may be more able to benefit from exercise, a skeletally mature population can also benefit from exercise programs aimed at increasing the functional loads to which the skeleton is exposed. The definitive explanation of mechanical-loading and (or) bone-cell mechanotransductive phenomena, however, remains elusive. Here, we briefly review the structural and anatomical foundation for bone adaptation, focusing on mechanical loading effects on bone, linked to the roles of integrins, cytoskeleton, membrane channels, and auto- and paracrine factors in bone modeling and remodeling.

Aging and the Osteogenic Response to Mechanical Loading

2001 ◽  
Vol 11 (s1) ◽  
pp. S137-S142 ◽  
Author(s):  
Wendy M. Kohrt
Keyword(s):  
Growth Factors ◽  
Bone Mass ◽  
Mechanical Loading ◽  
Bone Cells ◽  
Weight Bearing ◽  
Bone Modeling ◽  
Mineral Density ◽  
Increase Bone Mass ◽  
Age Related ◽  
Osteogenic Response

The osteogenic response to mechanical stress is blunted with aging. It has been postulated that this decline in responsiveness is related to (a) a limited ability to engender the strain necessary to reach the bone modeling threshold, due to decreased muscle mass and strength, and/or (b) a decline in certain hormones or growth factors that may interact with mechanical signals to change the sensitivity of bone cells to strain. There is reason to believe that both of these factors contribute to the reduced ability to increase bone mass through exercise with advancing age. Weight-bearing endurance exercise and resistance exercise have both been found to increase bone mass in older women and men. However, exercise training studies involving older individuals have generally resulted in increased bone mineral density only when the exercise is quite vigorous. There is also evidence that the osteogenic response to mechanical loading is enhanced by estrogens. Whether age-related changes in other factors (e.g., other hormones, growth factors, cytokines) also contribute to the reduced responsiveness of the aged skeleton to mechanical loading remains to be investigated.

Local Mineral and Matrix Changes Associated with Bone Adaptation and Microdamage

2005 ◽  
Vol 898 ◽  
Author(s):  
David H. Kohn ◽  
Nadder D. Sahar ◽  
Sun Ig Hong ◽  
Kurtulus Golcuk ◽  
Michael D. Morris
Keyword(s):  
Mechanical Loading ◽  
Chemical Properties ◽  
Fatigue Loading ◽  
Bone Adaptation ◽  
Extrinsic Factors ◽  
Intrinsic Factors ◽  
High Incidence ◽  
Insight Into ◽  
Skeletal Fracture

AbstractSkeletal fractures represent a significant medical and economic burden for society. It is generally thought that a high incidence of musculoskeletal fatigue loading results in damage accumulation at too high of a rate to be efficiently remodeled, leading to skeletal fracture. The state of damage in bone at a given time is therefore the net result of damage and repair processes, and is dependent upon extrinsic factors such as mechanical history, but also upon intrinsic factors, such as composition of bone mineral and matrix. In this invited paper, we review investigations on the coupling of Raman spectroscopy with mechanical loading of bone, providing insight into mechanisms of ultrastructural deformation in bone at smaller scales than previously understood. We also present new data showing that in-vivo mechanical loading results in increased resistance to fatigue damage, coupled with an increase in phosphate to amide I ratio and decrease in carbonate to phosphate ratio. Taken together, the data demonstrates the ability to modulate the mechanical and chemical properties of bone via exogenous mechanical stimulation.

The Search for Mechanism in Bone Adaptation Studies

2000 ◽  
Author(s):  
Stephen C. Cowin
Keyword(s):  
Mechanical Loading ◽  
Bone Structure ◽  
Three Dimensional ◽  
Cell System ◽  
Bone Adaptation ◽  
Bone Homeostasis ◽  
Adaptation Studies ◽  
Effector Cells ◽  
Dimensional Network ◽  
Strain Adaptation

Abstract The mechanosensory mechanisms in bone include (i) the cell system that is stimulated by external mechanical loading applied to the bone; (ii) the system that transduces that mechanical loading to a communicable signal; and (iii) the systems that transmit that signal to the effector cells for the maintenance of bone homeostasis and for strain adaptation of the bone structure. The effector cells are the osteoblasts and the osteoclasts. These systems and the mechanisms that they employ have not yet been unambiguously identified. The candidate systems are reviewed here. The current theoretical and experimental evidence, which suggests that osteocytes are the principal mechanosensory cells of bone, is summarized. This evidence shows that they are activated by shear stress from fluid flowing through the osteocyte canaliculi. The evidence also suggests that the electrically coupled three-dimensional network of osteocytes and lining cells is a communications system for the control of bone homeostasis and structural strain adaptation.

Flow-induced calcium oscillations in rat osteoblasts are age, loading frequency, and shear stress dependent

2001 ◽  
Vol 281 (5) ◽  
pp. C1635-C1641 ◽  
Author(s):  
Seth W. Donahue ◽  
Christopher R. Jacobs ◽  
Henry J. Donahue
Keyword(s):  
Shear Stress ◽  
Fluid Flow ◽  
Mechanical Loading ◽  
Cell Metabolism ◽  
Bone Cell ◽  
Bone Adaptation ◽  
Calcium Oscillations ◽  
Loading Frequency ◽  
Spontaneous Oscillations ◽  
Stress Dependent

Bone adaptation to mechanical loading is dependent on age and the frequency and magnitude of loading. It is believed that load-induced fluid flow in the porous spaces of bone is an important signal that influences bone cell metabolism and bone adaptation. We used fluid flow-induced shear stress as a mechanical stimulus to study intracellular calcium (Ca[Formula: see text]) signaling in rat osteoblastic cells (ROB) isolated from young, mature, and old animals. Fluid flow produced higher magnitude and more abundant [Ca2+]ioscillations than spontaneous oscillations, suggesting that flow-induced Ca[Formula: see text] signaling encodes a different cellular message than spontaneous oscillations. ROB from old rats showed less basal [Ca2+]i activity and were less responsive to fluid flow. Cells were more responsive to 0.2 Hz than to 1 or 2 Hz and to 2 Pa than to 1 Pa. These data suggest that the frequency and magnitude of mechanical loading may be encoded by the percentage of cells displaying [Ca2+]ioscillations but that the ability to transduce this information may be altered with age.

BONE ADAPTATION AND REGENERATION – NEW DEVELOPMENTS

2012 ◽  
Vol 17 ◽  
pp. 34-43 ◽  
Author(s):  
JENNEKE KLEIN-NULEND ◽  
ROMMEL GAUD BACABAC
Keyword(s):  
Bone Formation ◽  
Cell Signaling ◽  
Mechanical Loading ◽  
Bone Structure ◽  
Bone Cells ◽  
Mechanical Energy ◽  
Bone Adaptation ◽  
Mechanical Stimuli ◽  
Waste Products ◽  
Local Bone

Bone is a dynamic tissue that is constantly renewed and adapts to its local loading environment. Mechanical loading results in adaptive changes in bone size and shape that strengthen bone structure. The mechanisms for adaptation involve a multistep process called mechanotransduction, which is the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells. The transduction of a mechanical signal to a biochemical response involves pathways within the cell membrane and cytoskeleton of the osteocytes, the professional mechansensor cells of bone. During the last decade the role of mechanosensitive osteocytes in bone metabolism and turnover, and the lacuno-canalicular porosity as the structure that mediates mechanosensing, is likely to reveal a new paradigm for understanding the bone formation response to mechanical loading, and the bone resorption response to disuse. Strain-derived fluid flow of interstitial fluid through the lacuno-canalicular porosity seems to mechanically activate the osteocytes, as well as ensures transport of cell signaling molecules, nutrients and waste products. Cell-cell signaling from the osteocyte sensor cells to the effector cells (osteoblasts or osteoclasts), and the effector cell response – either bone formation or resorption, allow an explanation of local bone gain and loss as well as remodeling in response to fatigue damage as processes supervised by mechanosensitive osteocytes. The osteogenic activity of cultured bone cells has been quantitatively correlated with varying stress stimulations highlighting the importance of the rate of loading. Theoretically a possible mechanism for the stress response by osteocytes is due to strain amplification at the pericellular matrix. Single cell studies on molecular responses of osteocytes provide insight on local architectural alignment in bone during remodeling. Alignment seems to occur as a result of the osteocytes sensing different canalicular flow patterns around cutting cone and reversal zone during loading, thus determining the bone's structure. Disturbances in architecture and permeability of the 3D porous network will affect transduction of mechanical loads to the mechanosensors. Uncovering the cellular and mechanical basis of the osteocyte's response to loading represents a significant challenge to our understanding of cellular mechanotransduction and bone remodeling. In view of the importance of mechanical stress for maintaining bone strength, mechanical stimuli have great potential for providing a therapeutic approach for bone (re)generation.

Responses of Bone Cells to Biomechanical Forces in Vitro

1999 ◽  
Vol 13 (1) ◽  
pp. 93-98 ◽  
Author(s):  
E.H. Burger ◽  
J. Klein-Nulend
Keyword(s):  
Nitric Oxide ◽  
Mechanical Loading ◽  
Cell Biology ◽  
Cellular Response ◽  
Fluid Shear Stress ◽  
Bone Structure ◽  
Bone Cells ◽  
Bone Adaptation

In this paper, we review recent studies of the mechanism by which mechanical loading of bone is transduced into cellular signals of bone adaptation. Current biomechanical theory and in vivo as well as in vitro experiments agree that the three-dimensional network of osteocytes and bone-lining cells provides the cellular basis for mechanosensing in bone, leading to adaptive bone (re)modeling. They also agree that flow of interstitial fluid through the lacunar-canalicular porosity of bone, as a result of mechanical loading, most likely provides the stimulus for mechanosensing, and informs the bone cellular network about the adequacy of the existing bone structure. Important signaling molecules involved in in vivo adaptive bone formation, as well as in in vitro cellular response to fluid flow, are nitric oxide and prostaglandins. The expression of key enzymes for nitric oxide and prostaglandin production in bone cells is altered by fluid shear stress in vitro. Together, these studies have increased our understanding of the cell biology underlying Wolff's Law. This may lead to new strategies for combating disuse-related osteoporosis, and may also be of use in understanding and predicting the long-term integration of bone-replacing implants.

scholarly journals Simulated spaceflight produces a rapid and sustained loss of osteoprogenitors and an acute but transitory rise of osteoclast precursors in two genetic strains of mice

2012 ◽  
Vol 303 (11) ◽  
pp. E1354-E1362 ◽  
Author(s):  
Mohammad Shahnazari ◽  
Pam Kurimoto ◽  
Benjamin M. Boudignon ◽  
Benjamin E. Orwoll ◽  
Daniel D. Bikle ◽  
...  
Keyword(s):  
Bone Loss ◽  
Cancellous Bone ◽  
Bone Structure ◽  
Bone Cells ◽  
Weight Bearing ◽  
Bone Adaptation ◽  
Hindlimb Unloading ◽  
Skeletal Unloading ◽  
Precursor Pool ◽  
Cancellous Bone Structure

Loss of skeletal weight bearing or skeletal unloading as occurs during spaceflight inhibits bone formation and stimulates bone resorption. These are associated with a decline in the osteoblast (Ob.S/BS) and an increase in the osteoclast (Oc.S/BS) bone surfaces. To determine the temporal relationship between changes in the bone cells and their marrow precursor pools during sustained unloading, and whether genetic background influences these relationships, we used the hindlimb unloading model to induce bone loss in two strains of mice known to respond to load and having significantly different cancellous bone volumes (C57BL/6 and DBA/2 male mice). Skeletal unloading caused a progressive decline in bone volume that was accompanied by strain-specific changes in Ob.S/BS and Oc.S/BS. These were associated with a sustained reduction in the osteoprogenitor population and a dramatic but transient increase in the osteoclast precursor pool size in both strains. The results reveal that bone adaptation to skeletal unloading involves similar rapid changes in the osteoblast and osteoclast progenitor populations in both strains of mice but striking differences in Oc.S/BS dynamics, BFR, and cancellous bone structure. These strain-specific differences suggest that genetics plays an important role in determining the osteoblast and osteoclast populations on the bone surface and the dynamics of bone loss in response to skeletal unloading.

scholarly journals The Skeletal Cellular and Molecular Underpinning of the Murine Hindlimb Unloading Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Priyanka Garg ◽  
Maura Strigini ◽  
Laura Peurière ◽  
Laurence Vico ◽  
Donata Iandolo
Keyword(s):  
Bone Loss ◽  
Mechanical Loading ◽  
Weight Bearing ◽  
Bone Adaptation ◽  
Hindlimb Unloading ◽  
Molecular Pathways ◽  
Long Bones ◽  
Confounding Factors ◽  
Environmental Temperatures

Bone adaptation to spaceflight results in bone loss at weight bearing sites following the absence of the stimulus represented by ground force. The rodent hindlimb unloading model was designed to mimic the loss of mechanical loading experienced by astronauts in spaceflight to better understand the mechanisms causing this disuse-induced bone loss. The model has also been largely adopted to study disuse osteopenia and therefore to test drugs for its treatment. Loss of trabecular and cortical bone is observed in long bones of hindlimbs in tail-suspended rodents. Over the years, osteocytes have been shown to play a key role in sensing mechanical stress/stimulus via the ECM-integrin-cytoskeletal axis and to respond to it by regulating different cytokines such as SOST and RANKL. Colder experimental environments (~20–22°C) below thermoneutral temperatures (~28–32°C) exacerbate bone loss. Hence, it is important to consider the role of environmental temperatures on the experimental outcomes. We provide insights into the cellular and molecular pathways that have been shown to play a role in the hindlimb unloading and recommendations to minimize the effects of conditions that we refer to as confounding factors.

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