Osteocytes: a proposed multifunctional bone cell.
ABSTRACT Most cell types are ascribed a single function. The osteoclast holds the unique distinction of performing only one function in the body - that of resorbing bone. The osteoblast has been ascribed the major function of bone matrix production. Other less well-defined cell types include progenitor cells and the nebulous cell type that can support osteoclast formation upon stimulation with various bone resorbing cytokines. Obviously, these cells could have other functions. The definition of an osteocyte is descriptive of its location - cells surrounded by mineralized matrix - not its function. For this year's Sun Valley Workshop on osteocytes, several proposed functions will be presented. First, a general consensus exists that osteocytes are most likely sensitive to mechanotransduction and translate mechanical strain into biochemical signals. Consensus does not exist on the nature of the mechanical strain, the form of the biochemical signals, the target cell(s), or the viability status of the osteocyte. Second, it is also proposed that this cell is incredibly adaptable and expresses plasticity in response to mechanical stimuli. In other words, this cell can readjust its responses to strain in the presence of other bone agents such as hormones and bone factors. Third, it will also be presented that osteocytes maintain systemic mineral homeostasis by regulating mineral release and deposition over the enormous surface area over which these cells interface with the surrounding matrix. Although osteocytes are terminally differentiated osteoblasts, they appear to have separate and distinct properties from their predecessors. Bone cell biologists loaded with an arsenal of bone anabolic and catabolic factors are examining the expression and effects of these factors on osteocytes. Engineers trained in mathematical modeling have generated new models of strain and connectivity to be tested. The unique morphology of osteocytes suggests that the cytoskeleton in these cells may function differently from osteoblasts and other cell types. Osteocytes may consist of different subpopulations; some that possess receptors for parathyroid hormone (PTH) and others that only express receptors for carboxyl terminal PTH suggesting different functions and responses. Osteocytes may respond rapidly to strain through glutamate receptor-like mechanisms, through calcium influxes, through gap junctions, and less rapidly through the production of small molecules and factors. Strain may take the form of substrate stretching and/or fluid flow. Osteocytes may communicate with other osteocytes and/or bone surface cells such as lining cells, stromal cells, osteoblasts, and/or osteoclasts and their precursors. The viability status of the osteocyte may determine the type of signals sent from these cells. If the cells are deprived of oxygen or nutrients, the apoptotic cells may send signals for initiation of resorption. If the cells and/or their dendritic process are ripped or torn by microdamage, they may send signals of both resorption and formation. If the majority of these theories are correct, then the osteocyte is the 'smart' cell that can direct or orchestrate the bone resorbing and bone forming cells even in its death and dying.
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ABSTRACT: The purpose of this study was to evaluate the influence of reusing high-resistance drills on bone heating, immediate bone cell viability, and drill wear after performing implant osteotomies in rabbit tibias. Two hundred sequential implant osteotomies were created in the superior tibial cortex of 12 White male rabbits. Six groups were established (G1 to G6) according to the number of osteotomies performed with each drill (0, 10, 20, 30, 40, and 50). Drilling began with a spear drill, followed by 2.0-mm, 2.8-mm, 3.0-mm, and 3.15-mm helical drills. The receptor beds were collected for immunohistochemical analysis, thermal changes were quantified, and the drills were subjected to scanning electron microscopy analysis. A high degree of correlation between drill wear and number of osteotomies was observed (Pearson correlation coefficient, r = 0.984). Spear drills underwent twice as much deformation as helical drills. The bone heating analysis concluded that there was no statistically significant relationship between the number of osteotomies and bone heating (P > .05), but there were greater thermal changes during drilling with the spear drill than during drilling with helical drills (ratio 3:1). Immunohistochemical analysis showed a physiologic balance of osteoprotegerin and RANKL (receptor activator of nuclear factor κB ligand) immunolabeling in all groups; however, there was greater immunolabeling of all proteins in group G6 (50 osteotomies). The tested drills did not cause significant bone heating after being reused 50 times; however, they caused more tissue trauma in the 50th osteotomy. Worn drills that are reused may be expected to cause excessive damage to the bone tissue and could adversely affect the osseointegration process.The International journal of oral & maxillofacial implants 11/2011; 26(6):1193-201. · 1.91 Impact Factor
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ABSTRACT: The proliferative impulse of the growth plate cartilage and related structures and its effect on the dimensions of long bones are well documented. The modulation of shape, however, is less known, and in general, it is referred to the coupled resorption/apposition process of bone modelling. A morphometric study was carried out on rabbit tibiae comparing size increments and shape changes in relation to age. Utilizing measurements made using dried bones, radiography and computerized tomography, it was possible to perform a three-dimensional analysis of shape modulation occurring during a period of growth extending from 3 months to 1 year of age. The dynamics of the shape changes related to growth were studied with a fluorescent tetracycline labelling. This enabled correlation of shape modulation with the 3-D distribution of apposition and resorption. The current thinking behind the influences and mechanical forces affecting bone architecture was discussed in the light of these findings. Several factors play a role in the structural organization of the human and upper vertebrates' skeleton, whose shape is genetically determined in the complex process usually referred as 'modelling'. This does not conflict with the existing evidence of remodelling being influenced by mechanical stimuli, but the unsolved question remains how physical forces (strains) act on the biological substrate of cartilage and bone cells.Anantomia Histologia Embryologia 01/2012; 41(3):217-26. · 0.88 Impact Factor
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ABSTRACT: Cyclic mechanical loading is perhaps the most important physiological factor regulating bone mass and shape in a way which balances optimal strength with minimal weight. This bone adaptation process spans multiple length and time scales. Forces resulting from physiological exercise at the organ scale are sensed at the cellular scale by osteocytes, which reside inside the bone matrix. Via biochemical pathways, osteocytes orchestrate the local remodeling action of osteoblasts (bone formation) and osteoclasts (bone resorption). Together these local adaptive remodeling activities sum up to strengthen bone globally at the organ scale. To resolve the underlying mechanisms it is required to identify and quantify both cause and effect across the different scales. Progress has been made at the different scales experimentally. Computational models of bone adaptation have been developed to piece together various experimental observations at the different scales into coherent and plausible mechanisms. However additional quantitative experimental validation is still required to build upon the insights which have already been achieved. In this review we discuss emerging as well as state of the art experimental and computational techniques and how they might be used in a mechanical systems biology approach to further our understanding of the mechanisms governing load induced bone adaptation, i.e., ways are outlined in which experimental and computational approaches could be coupled, in a quantitative manner to create more reliable multiscale models of bone.Annals of biomedical engineering 05/2012; 40(11):2475-87. · 2.41 Impact Factor