The Search for Mechanism in Bone Adaptation Studies

2000 ◽  
Author(s):  
Stephen C. Cowin

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.

2006 ◽  
Vol 31 (6) ◽  
pp. 655-660 ◽  
Author(s):  
Ronald Zernicke ◽  
Christopher MacKay ◽  
Caeley Lorincz

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.


Author(s):  
JENNEKE KLEIN-NULEND ◽  
ROMMEL GAUD BACABAC

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.


1999 ◽  
Vol 13 (1) ◽  
pp. 93-98 ◽  
Author(s):  
E.H. Burger ◽  
J. Klein-Nulend

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.


2020 ◽  
Vol 10 (2) ◽  
pp. 133-148
Author(s):  
Ankaj Kaundal ◽  
Pravin Kumar ◽  
Rajendra Awasthi ◽  
Giriraj T. Kulkarni

Aim: The study was aimed to develop mucoadhesive buccal tablets using Aster ericoides leaves mucilage. Background : Mucilages are naturally occurring high-molecular-weight polyuronides, which have been extensively studied for their application in different pharmaceutical dosage forms. Objective: The objective of the present research was to establish the mucilage isolated from the leaves of Aster ericoides as an excipient for the formulation of the mucoadhesive buccal tablet. Method: The mucilage was isolated from the leaves of Aster ericoides by maceration, precipitated with acetone and characterized. Tablets were prepared using wet granulation technique and evaluated for various official tests. Results: The mucilage was found to be non-toxic on A-431 and Vero cell lines. It was insoluble but swellable in cold and hot water. The results indicate that mucilage can form a three-dimensional network. The pH of the mucilage (6.82 ± 0.13) indicated that it might be non-irritant to the buccal cavity. The mucilage was found to be free from microbes. The release of drug was by Fickian diffusion. The in vivo buccal tablet acceptance was 80%. No significant difference between the diastolic blood pressure of standard and Aster tablets treated volunteer group was recorded. Conclusion: The mucilage was found to be non-toxic on A-431 and Vero cell lines. It was insoluble but swellable in cold and hot water. The results indicate that mucilage can form a three-dimensional network. The pH of the mucilage (6.82 ± 0.13) indicated that it might be non-irritant to the buccal cavity. The mucilage was found to be free from microbes. The release of drug was by Fickian diffusion. The in vivo buccal tablet acceptance was 80%. No significant difference between the diastolic blood pressure of standard and Aster tablets treated volunteer group was recorded. Other: However, to prove the potency of the polymer, in vivo bioavailability studies in human volunteers are needed along with chronic toxicity studies in suitable animal models.


2014 ◽  
Vol 70 (9) ◽  
pp. i46-i46 ◽  
Author(s):  
Matthias Weil ◽  
Thomas Häusler

The crystal structure of the room-temperature modification of K[Hg(SCN)3], potassium trithiocyanatomercurate(II), was redetermined based on modern CCD data. In comparison with the previous report [Zhdanov & Sanadze (1952).Zh. Fiz. Khim.26, 469–478], reliability factors, standard deviations of lattice parameters and atomic coordinates, as well as anisotropic displacement parameters, were revealed for all atoms. The higher precision and accuracy of the model is, for example, reflected by the Hg—S bond lengths of 2.3954 (11), 2.4481 (8) and 2.7653 (6) Å in comparison with values of 2.24, 2.43 and 2.77 Å. All atoms in the crystal structure are located on mirror planes. The Hg2+cation is surrounded by four S atoms in a seesaw shape [S—Hg—S angles range from 94.65 (2) to 154.06 (3)°]. The HgS4polyhedra share a common S atom, building up chains extending parallel to [010]. All S atoms of the resulting1∞[HgS2/1S2/2] chains are also part of SCN−anions that link these chains with the K+cations into a three-dimensional network. The K—N bond lengths of the distorted KN7polyhedra lie between 2.926 (2) and 3.051 (3) Å.


Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1841
Author(s):  
Kang Li ◽  
Xuejie Zhang ◽  
Yan Qin ◽  
Ying Li

Aerogels have been widely used in the adsorption of pollutants because of their large specific surface area. As an environmentally friendly natural polysaccharide, cellulose is a good candidate for the preparation of aerogels due to its wide sources and abundant polar groups. In this paper, an approach to construct cellulose nanofibers aerogels with both the good mechanical property and the high pollutants adsorption capability through chemical crosslinking was explored. On this basis, TiO2 nanoparticles were loaded on the aerogel through the sol-gel method followed by the hydrothermal method, thereby the enriched pollutants in the aerogel could be degraded synchronously. The chemical cross-linker not only helps build the three-dimensional network structure of aerogels, but also provides loading sites for TiO2. The degradation efficiency of pollutants by the TiO2@CNF Aerogel can reach more than 90% after 4 h, and the efficiency is still more than 70% after five cycles. The prepared TiO2@CNF Aerogels have high potential in the field of environmental management, because of the high efficiency of treating organic pollutes and the sustainability of the materials. The work also provides a choice for the functional utilization of cellulose, offering a valuable method to utilize the large amount of cellulose in nature.


RSC Advances ◽  
2021 ◽  
Vol 11 (33) ◽  
pp. 20446-20456
Author(s):  
Xi Ma ◽  
Ziwei Wang ◽  
Haoguo Yang ◽  
Yiqiu Zhang ◽  
Zizhong Zhang ◽  
...  

Compared with traditional layered graphene, graphene hydrogels have been used to construct highly efficient visible light-excited photocatalysts due to their particular three-dimensional network structure and efficient electron transport capacity.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Angad Malhotra ◽  
Matthias Walle ◽  
Graeme R. Paul ◽  
Gisela A. Kuhn ◽  
Ralph Müller

AbstractMethods to repair bone defects arising from trauma, resection, or disease, continue to be sought after. Cyclic mechanical loading is well established to influence bone (re)modelling activity, in which bone formation and resorption are correlated to micro-scale strain. Based on this, the application of mechanical stimulation across a bone defect could improve healing. However, if ignoring the mechanical integrity of defected bone, loading regimes have a high potential to either cause damage or be ineffective. This study explores real-time finite element (rtFE) methods that use three-dimensional structural analyses from micro-computed tomography images to estimate effective peak cyclic loads in a subject-specific and time-dependent manner. It demonstrates the concept in a cyclically loaded mouse caudal vertebral bone defect model. Using rtFE analysis combined with adaptive mechanical loading, mouse bone healing was significantly improved over non-loaded controls, with no incidence of vertebral fractures. Such rtFE-driven adaptive loading regimes demonstrated here could be relevant to clinical bone defect healing scenarios, where mechanical loading can become patient-specific and more efficacious. This is achieved by accounting for initial bone defect conditions and spatio-temporal healing, both being factors that are always unique to the patient.


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