Osteocytes as a record of bone formation dynamics: A mathematical model of osteocyte generation in bone matrix

The formation of new bone involves both the deposition of bone matrix, and the formation of a network of cells embedded within the bone matrix, called osteocytes. Osteocytes derive from bone-synthesising cells (osteoblasts) that become buried in bone matrix during bone deposition. The generation of osteocytes is a complex process that remains incompletely understood. Whilst osteoblast burial determines the density of osteocytes, the expanding network of osteocytes regulates in turn osteoblast activity and osteoblast burial. In this paper, a spatiotemporal continuous model is proposed to investigate the osteoblast-to-osteocyte transition. The aims of the model are (i) to link dynamic properties of osteocyte generation with properties of the osteocyte network imprinted in bone, and (ii) to investigate Marotti's hypothesis that osteocytes prompt the burial of osteoblasts when they become covered with sufficient bone matrix. Osteocyte density is assumed in the model to be generated at the moving bone surface by a combination of osteoblast density, matrix secretory rate, rate of entrapment, and curvature of the bone substrate, but is found to be determined solely by the ratio of the instantaneous burial rate and matrix secretory rate. Osteocyte density does not explicitly depend on osteoblast density nor curvature. Osteocyte apoptosis is also included to distinguish between the density of osteocyte lacuna and the density of live osteocytes. Experimental measurements of osteocyte lacuna densities are used to estimate the rate of burial of osteoblasts in bone matrix. These results suggest that: (i) burial rate decreases during osteonal infilling, and (ii) the control of osteoblast burial by osteocytes is likely to emanate as a collective signal from a large group of osteocytes, rather than from the osteocytes closest to the bone deposition front.Comment: 11 pages, 6 figures. V2: substantially augmented version. Addition of Section 4 (osteocyte apoptosis

Governing equations of tissue modelling and remodelling: A unified generalised description of surface and bulk balance

Several biological tissues undergo changes in their geometry and in their bulk material properties by modelling and remodelling processes. Modelling synthesises tissue in some regions and removes tissue in others. Remodelling overwrites old tissue material properties with newly formed, immature tissue properties. As a result, tissues are made up of different "patches", i.e., adjacent tissue regions of different ages and different material properties, within evolving boundaries. In this paper, generalised equations governing the spatio-temporal evolution of such tissues are developed within the continuum model. These equations take into account nonconservative, discontinuous surface mass balance due to creation and destruction of material at moving interfaces, and bulk balance due to tissue maturation. These equations make it possible to model patchy tissue states and their evolution without explicitly maintaining a record of when/where resorption and formation processes occurred. The time evolution of spatially averaged tissue properties is derived systematically by integration. These spatially-averaged equations cannot be written in closed form as they retain traces that tissue destruction is localised at tissue boundaries. The formalism developed in this paper is applied to bone tissues, which exhibit strong material heterogeneities due to their slow mineralisation and remodelling processes. Evolution equations are proposed in particular for osteocyte density and bone mineral density. Effective average equations for bone mineral density (BMD) and tissue mineral density (TMD) are derived using a mean-field approximation. The error made by this approximation when remodelling patchy tissue is investigated. The specific time signatures of BMD or TMD during remodelling events may provide a way to detect these events occurring at lower, unseen spatial resolutions from microCT scans.Comment: 14 pages, 8 figures. V2: minor stylistic changes, more detailed derivation of Eqs (30)-(31), additional comments on implication of BMD and TMD signatures for microCT scan

The Casimir Effect

After a review of the standard calculation of the Casimir force between two metallic plates at zero and non-zero temperatures, we present the study of microscopic models to determine the large-distance asymptotic force in the high-temperature regime. Casimir's conducting plates are modelized by plasmas of interacting charges at temperature T. The charges are either classical, or quantum-mechanical and coupled to a (classical) radiation field. In these models, the force obtained is twice weaker than that arising from standard treatments neglecting the microscopic charge fluctutations inside the bodies. The enforcement of inert boundary conditions on the field in the usual calculations turns out to be inadequate in this regime. Other aspects of dispersion forces are also reviewed. The status of (non-retarded) van der Waals-London forces in a dilute medium of non-zero temperature and density is investigated. In a proper scaling regime called the atomic limit (high dilution and low temperature), one is able to give the exact large-distance atomic correlations up to exponentially small terms as T->0. Retarded van der Waals forces and forces between dielectric bodies are also reviewed. Finally, the Casimir effect in critical phenomena is addressed by considering the free Bose gas. It is shown that the grand-canonical potential of the gas in a slab at the critical value of the chemical potential has finite size corrections of the standard Casimir type. They can be attributed to the existence of long-range order generated by gapless excitations in the phase with broken continuous symmetry.Comment: Lecture notes prepared for the proceedings of the 1st Warsaw School of Statistical Physics, Kazimierz, Poland, June 2005. To appear in Acta Physica Polonica (2006). 52 pages, 0 figures. Available at http://th-www.if.uj.edu.pl/acta/vol37/pdf/v37p2503.pd

Osteoblasts infill irregular pores under curvature and porosity controls: A hypothesis-testing analysis of cell behaviours

The geometric control of bone tissue growth plays a significant role in bone remodelling, age-related bone loss, and tissue engineering. However, how exactly geometry influences the behaviour of bone-forming cells remains elusive. Geometry modulates cell populations collectively through the evolving space available to the cells, but it may also modulate the individual behaviours of cells. To factor out the collective influence of geometry and gain access to the geometric regulation of individual cell behaviours, we develop a mathematical model of the infilling of cortical bone pores and use it with available experimental data on cortical infilling rates. Testing different possible modes of geometric controls of individual cell behaviours consistent with the experimental data, we find that efficient smoothing of irregular pores only occurs when cell secretory rate is controlled by porosity rather than curvature. This porosity control suggests the convergence of a large scale of intercellular signalling to single bone-forming cells, consistent with that provided by the osteocyte network in response to mechanical stimulus. After validating the mathematical model with the histological record of a real cortical pore infilling, we explore the infilling of a population of randomly generated initial pore shapes. We find that amongst all the geometric regulations considered, the collective influence of curvature on cell crowding is a dominant factor for how fast cortical bone pores infill, and we suggest that the irregularity of cement lines thereby explains some of the variability in double labelling data as well as the overall speed of osteon infilling.Comment: 14 pages, 11 figures, Appendi

HST observations of the limb polarization of Titan

Titan is an excellent test case for detailed studies of the scattering polarization from thick hazy atmospheres. We present the first limb polarization measurements of Titan, which are compared as a test to our limb polarization models. Previously unpublished imaging polarimetry from the HST archive is presented which resolves the disk of Titan. We determine flux-weighted averages of the limb polarization and radial limb polarization profiles, and investigate the degradation and cancelation effects in the polarization signal due to the limited spatial resolution of our observations. Taking this into account we derive corrected values for the limb polarization in Titan. The results are compared with limb polarization models, using atmosphere and haze scattering parameters from the literature. In the wavelength bands between 250 nm and 2000 nm a strong limb polarization of about 2-7 % is detected with a position angle perpendicular to the limb. The fractional polarization is highest around 1 micron. As a first approximation, the polarization seems to be equally strong along the entire limb. The detected polarization is compatible with expectations from previous polarimetric observations taken with Voyager 2, Pioneer 11, and the Huygens probe. Our results indicate that ground-based monitoring measurements of the limb-polarization of Titan could be useful for investigating local haze properties and the impact of short-term and seasonal variations of the hazy atmosphere of Titan. Planets with hazy atmospheres similar to Titan are particularly good candidates for detection with the polarimetric mode of the upcoming planet finder instrument at the VLT. Therefore, a good knowledge of the polarization properties of Titan is also important for the search and investigation of extra-solar planets.Comment: 13 pages, 13 figures, accepted for publication in Astronomy & Astrophysic

A van der Waals free energy in electrolytes revisited

A system of three electrolytes separated by two parallel planes is considered. Each region is described by a dielectric constant and a Coulomb fluid in the Debye-H\"uckel regime. In their book Dispersion Forces, Mahanty and Ninham have given the van der Waals free energy of this system. We rederive this free energy by a different method, using linear response theory and the electrostatic Maxwell stress tensor for obtaining the dispersion force.Comment: 7 pages. PACS numbers updated. References update

A multiscale mechanobiological model of bone remodelling predicts site-specific bone loss in the femur during osteoporosis and mechanical disuse

We propose a multiscale mechanobiological model of bone remodelling to investigate the site-specific evolution of bone volume fraction across the midshaft of a femur. The model includes hormonal regulation and biochemical coupling of bone cell populations, the influence of the microstructure on bone turnover rate, and mechanical adaptation of the tissue. Both microscopic and tissue-scale stress/strain states of the tissue are calculated from macroscopic loads by a combination of beam theory and micromechanical homogenisation. This model is applied to simulate the spatio-temporal evolution of a human midshaft femur scan subjected to two deregulating circumstances: (i) osteoporosis and (ii) mechanical disuse. Both simulated deregulations led to endocortical bone loss, cortical wall thinning and expansion of the medullary cavity, in accordance with experimental findings. Our model suggests that these observations are attributable to a large extent to the influence of the microstructure on bone turnover rate. Mechanical adaptation is found to help preserve intracortical bone matrix near the periosteum. Moreover, it leads to non-uniform cortical wall thickness due to the asymmetry of macroscopic loads introduced by the bending moment. The effect of mechanical adaptation near the endosteum can be greatly affected by whether the mechanical stimulus includes stress concentration effects or not.Comment: 25 pages, 10 figure

Microscopic Origin of Universality in Casimir Forces

The microscopic mechanisms for universality of Casimir forces between macroscopic conductors are displayed in a model of classical charged fluids. The model consists of two slabs in empty space at distance d containing classical charged particles in thermal equilibrium (plasma, electrolyte). A direct computation of the average force per unit surface yields, at large distance, the usual form of the Casimir force in the classical limit (up to a factor 2 due to the fact that the model does not incorporate the magnetic part of the force). Universality originates from perfect screening sum rules obeyed by the microscopic charge correlations in conductors. If one of the slabs is replaced by a macroscopic dielectric medium, the result of Lifshitz theory for the force is retrieved. The techniques used are Mayer expansions and integral equations for charged fluid