ترغب بنشر مسار تعليمي؟ اضغط هنا

The Small World of Osteocytes: Connectomics of the Lacuno-Canalicular Network in Bone

63   0   0.0 ( 0 )
 نشر من قبل Philip Kollmannsberger
 تاريخ النشر 2017
  مجال البحث فيزياء علم الأحياء
والبحث باللغة English




اسأل ChatGPT حول البحث

Osteocytes and their cell processes reside in a large, interconnected network of voids pervading the mineralized bone matrix of most vertebrates. This osteocyte lacuno-canalicular network (OLCN) is believed to play important roles in mechanosensing, mineral homeostasis, and for the mechanical properties of bone. While the extracellular matrix structure of bone is extensively studied on ultrastructural and macroscopic scales, there is a lack of quantitative knowledge on how the cellular network is organized. Using a recently introduced imaging and quantification approach, we analyze the OLCN in different bone types from mouse and sheep that exhibit different degrees of structural organization not only of the cell network but also of the fibrous matrix deposited by the cells. We define a number of robust, quantitative measures that are derived from the theory of complex networks. These measures enable us to gain insights into how efficient the network is organized with regard to intercellular transport and communication. Our analysis shows that the cell network in regularly organized, slow-growing bone tissue from sheep is less connected, but more efficiently organized compared to irregular and fast-growing bone tissue from mice. On the level of statistical topological properties (edges per node, edge length and degree distribution), both network types are indistinguishable, highlighting that despite pronounced differences at the tissue level, the topological architecture of the osteocyte canalicular network at the subcellular level may be independent of species and bone type. Our results suggest a universal mechanism underlying the self-organization of individual cells into a large, interconnected network during bone formation and mineralization.

قيم البحث

اقرأ أيضاً

Until recently many studies of bone remodeling at the cellular level have focused on the behavior of mature osteoblasts and osteoclasts, and their respective precursor cells, with the role of osteocytes and bone lining cells left largely unexplored. This is particularly true with respect to the mathematical modeling of bone remodeling. However, there is increasing evidence that osteocytes play important roles in the cycle of targeted bone remodeling, in serving as a significant source of RANKL to support osteoclastogenesis, and in secreting the bone formation inhibitor sclerostin. Moreover, there is also increasing interest in sclerostin, an osteocyte-secreted bone formation inhibitor, and its role in regulating local response to changes in the bone microenvironment. Here we develop a cell population model of bone remodeling that includes the role of osteocytes, sclerostin, and allows for the possibility of RANKL expression by osteocyte cell populations. This model extends and complements many of the existing mathematical models for bone remodeling but can be used to explore aspects of the process of bone remodeling that were previously beyond the scope of prior modeling work. Through numerical simulations we demonstrate that our model can be used to theoretically explore many of the most recent experimental results for bone remodeling, and can be utilized to assess the effects of novel bone-targeting agents on the bone remodeling process.
We develop a heuristic model embedding Kleiber and Murray laws to describe mass growth, metastasis and vascularization in cancer. We analyze the relevant dynamics using different evolution equations (Verhulst, Gompertz and others). Their extension to reaction diffusion equation of the Fisher type is then used to describe the relevant metastatic spreading in space. Regarding this last point, we suggest that cancer diffusion may be regulated by Levy flights mechanisms and discuss the possibility that the associated reaction diffusion equations are of the fractional type, with the fractional coefficient being determined by the fractal nature of the capillary evolution.
Multiple myeloma is a plasma cell cancer that leads to a dysregulated bone remodeling process. We present a partial differential equation model describing the dynamics of bone remodeling with the presence of myeloma tumor cells. The model explicitly takes into account the roles of osteoclasts, osteoblasts, precursor cells, stromal cells, osteocytes, and tumor cells. Previous models based on ordinary differential equations make the simplifying assumption that the bone and tumor cells are adjacent to each other. However, in actuality, these cell populations are separated by the bone marrow. Our model takes this separation into account by including the diffusion of chemical factors across the marrow, which can be viewed as communication between the tumor and bone. Additionally, this model incorporates the growth of the tumor and the diminishing bone mass by utilizing a ``moving boundary. We present numerical simulations that qualitatively validate our models description of the cell population dynamics.
Radiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Hyperthermia (HT) is a promising option to improve the outcome of radiation treatment (RT) and is increasingly applied in hospital. However, the synergistic effect of simultaneous thermoradiotherapy is not well understood yet, while its mathematical modelling is essential for treatment planning. To better understand this synergy, we propose a theoretical model in which the thermal enhancement ratio (TER) is explained by the fraction of cells being radiosensitised by the infliction of sublethal damage through mild HT. Further damage finally kills the cell or inhibits its proliferation in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our predictions well reproduce experimental data from in-vitro and in-vivo studies, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.
170 - Pascal R Buenzli 2014
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 Marottis 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.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا