269 research outputs found
The Small World of Osteocytes: Connectomics of the Lacuno-Canalicular Network in Bone
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
Fragility of bone material controlled by internal interfaces
Bone material is built in a complex multiscale arrangement of mineralized collagen fibrils containing water, proteoglycans and some noncollagenous proteins. This organization is not static as bone is constantly remodeled and thus able to repair damaged tissue and adapt to the loading situation. In preventing fractures, the most important mechanical property is toughness, which is the ability to absorb impact energy without reaching complete failure. There is no simple explanation for the origin of the toughness of bone material, and this property depends in a complex way on the internal architecture of the material on all scales from nanometers to millimeters. Hence, fragility may have different mechanical origins, depending on which toughening mechanism is not working properly. This article reviews the toughening mechanisms described for bone material and attempts to put them in a clinical context, with the hope that future analysis of bone fragility may be guided by this collection of possible mechanistic origins
Understanding hierarchy and functions of bone using scanning x-ray scattering methods
International audienceBiological materials are often hierarchically structured from the nanometer to the macroscopic scale. Specific characterization methods are needed to characterize the structures at these different length scales. This chapter reviews -based on the example of bone- the use of X-ray scattering methods to explore representative and quantitative structure information as well as structure-function relations in hierarchically structured biological materials. X-ray scattering techniques are particularly well suited for the characterization of the form and organization of organic and inorganic components in those materials. When nanometer-sized structures are exposed to X-rays, details of the internal material structure can be revealed by the analysis of the resulting interference patterns. Fundamental aspects of wide and small angle X-ray scattering (WAXS and SAXS) are discussed with specific focus on bone studies. An important field of research using X-ray scattering techniques, is the in situ combination with mechanical testing, which allows investigating changes in structure under specific loading conditions. Another common application is the structural study of heterogeneities or local structures within a sample using a narrow focused X-ray beam. Furthermore, in scanning mode, where the specimen is displaced step by step across a microbeam while collecting a SAXS/WAXS pattern at each step, complex structural maps of the sample can be derived. A natural extension of the method toward imaging is described in the context of X-ray imaging with scattering contrast
Springback effect and structural features during the drying of silica aerogels tracked by in-situ synchrotron X-ray scattering
The springback effect during ambient pressure drying of aerogels is an interesting structural phenomenon, consisting of a severe shrinkage followed by almost complete re-expansion. The drying of gels causes shrinkage, whereas re-expansion is believed to be linked to repelling forces on the nanoscale. A multi-scale structural characterization of this significant volume change is key in controlling aerogel processing and properties. In this work, hydrophobic, monolithic silica aerogels with high specific surface areas were synthesized by modification with trimethylchlorosilane and ambient pressure drying. Here, we report a multi-method approach focusing on in-situ X-ray scattering to observe alterations of the nanostructured material during the drying of surface-modified and unmodified silica gels. Both show a porous fractal nanostructure, which partially collapses during drying and only recovers in surface-modified samples during the springback effect. Distinct changes of the X-ray scattering data were reproducibly associated with the shrinkage, re-expansion and drying of the gel network. Our findings may contribute to tailor aerogels with specific functionality, as the springback effect has a direct influence on properties (e.g., porosity, pore size distribution), which is directly affected by the degree of re-expansion
Evidence for an elementary process in bone plasticity with an activation enthalpy of 1âeV
The molecular mechanisms for plastic deformation of bone tissue are not well understood. We analysed temperature and strain-rate dependence of the tensile deformation behaviour in fibrolamellar bone, using a technique originally developed for studying plastic deformation in metals. We show that, beyond the elastic regime, bone is highly strain-rate sensitive, with an activation volume of ca 0.6ânm3. We find an activation energy of 1.1âeV associated with the basic step involved in the plastic deformation of bone at the molecular level. This is much higher than the energy of hydrogen bonds, but it is lower than the energy required for breaking covalent bonds inside the collagen fibrils. Based on the magnitude of these quantities, we speculate that disruption of electrostatic bonds between polyelectrolyte molecules in the extrafibrillar matrix of bone, perhaps mediated by polyvalent ions such as calcium, may be the rate-limiting elementary step in bone plasticity
Breast cancerâsecreted factors perturb murine bone growth in regions prone to metastasis
Breast cancer frequently metastasizes to bone, causing osteolytic lesions. However, how factors secreted by primary tumors affect the bone microenvironment before the osteolytic phase of metastatic tumor growth remains unclear. Understanding these changes is critical as they may regulate metastatic dissemination and progression. To mimic premetastatic bone adaptation, immunocompromised mice were injected with MDA-MB-231âconditioned medium [tumor-conditioned media (TCM)]. Subsequently, the bones of these mice were subjected to multiscale, correlative analysis including RNA sequencing, histology, microâcomputed tomography, x-ray scattering analysis, and Raman imaging. In contrast to overt metastasis causing osteolysis, TCM treatment induced new bone formation that was characterized by increased mineral apposition rate relative to control bones, altered bone quality with less matrix and more carbonate substitution, and the deposition of disoriented mineral near the growth plate. Our study suggests that breast cancerâsecreted factors may promote perturbed bone growth before metastasis, which could affect initial seeding of tumor cells
A 3D network of nanochannels for possible ion and molecule transit in mineralizing bone and cartilage
During crucial growth stages of vertebrate long bones, calcified cartilage beneath the growth plate is anchored to bone by a third mineralized component, the cement line. Proper skeletal development is contingent on the interplay of these three constituents, yet their mineralization processes and structural interactions are incompletely understood, in part from limited knowledge of their meso- and nanoscale features. Herein, focused ion beam-scanning electron microscopy (FIB-SEM) with serial surface imaging is applied to examine the cartilageâbone interface of mouse femoral heads at an unprecedented scale: FIB-SEM provides 3D, nanometer resolution of structural details for volumes encompassing metaphyseal calcified cartilage, bone, and the intervening cement line. A novel and complex structural network is revealed, comprising densely packed nanochannels smaller than bone canaliculi (â10â50ânm diameter) within the calcified cartilage and bone extracellular matrices, but absent in the cement line. A structural correlation is demonstrated between the nanochannels and ellipsoidal mineral domains, which appear to coalesce during mineralization in a process analogous to powder sintering in metallurgy. A mineralization process is proposed, supported by energy-dispersive X-Ray spectroscopy of nanochannel contents, in which these unreported structures offer ion and molecule conduits to access the extracellular matrices of calcified cartilage and bone
Dendritic polyglycerol anions for the selective targeting of native and inflamed articular cartilage
The destruction of articular cartilage is a critical feature in joint diseases. An approach to selectively target the damaged tissue is promising for the development of diagnostic and therapeutic agents. We herein present the interaction of dendritic polyglycerol (dPG) anions with native and inflamed cartilage. Confocal laser scanning microscopy revealed the inert character of dPG and low functionalized dPG bisphosphonate (dPGBP7%) toward cartilage in vitro. An enhanced binding was observed for highly functionalized dPG bisphosphonate, sulfate, and phosphate, which additionally showed a higher affinity to IL-1ÎČ treated tissue. The mixed anion containing sulfate and bisphosphonate groups exhibited an exceptionally high affinity to cartilage and strongly bound to collagen type II, as shown by a normalized fluorescence-based binding assay. All polyglycerol anions, except dPGBP7%, were taken up by chondrocytes within 24 h and no cytotoxicity was found up to 10â5 M. In a rheumatoid arthritis model, dPGBP7% accumulated in mineralized compartments of inflamed joints and showed an increasing affinity to cartilage with higher clinical scores, as evident from histological examinations. For dPGS no interaction with bone but a strong binding to cartilage, independent of the score, was demonstrated. These results make dPG anions promising candidates for the selective targeting of cartilage tissue
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