The Role of Water in Bone Nanohydroxyapatite Nucleation

In a previous study of the deposition of nanohydroxyapatite on demineralized cortical bone collagen stimulated by deformation-induced piezoelectricity was obtained in our lab. Thus, the aim of the present study was to characterize the interactions between the self-assembled nanostructure of bone collagen and water in presence and absence of hydroxyapatite (HAP) to elucidate which factors allowed such deposition in just four weeks without the presence of bone cells. It was found that the loss of the mineral phase in bone (HAP) contributes to decrease the thermal stability of the collagen nanostructures. An important increase on the free, bonded and structural water content was found in the bone matrix, directly related to the degree of demineralization reached by the collagen matrix with time. This demonstrates that the collagen nanostructure is able to restructure itself while losing the interactions with the mineral phase, establishing new interactions with the water molecule, orienting the dipoles of the collagen molecule. All these increase the piezoelectric character of the bone matrix and allows the collagen matrix to get prepared for a bone re-mineralization process without bone cells, due to the electrostatic interactions established with the calcium and phosphate ions of the external fluid of the extracellular matrix.

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Collagen-the Ultrastructural Element of the Bone Matrix

Revista de Chimie ◽

10.37358/rc.18.7.6400 ◽

2018 ◽

Vol 69 (7) ◽

pp. 1706-1709

Author(s):

Nicoleta Dumitru ◽

Andra Cocolos ◽

Andra Caragheorgheopol ◽

Constantin Dumitrache ◽

Ovidiu Gabriel Bratu ◽

...

Keyword(s):

Type I Collagen ◽

Bone Microarchitecture ◽

Complex Structure ◽

Bone Matrix ◽

Organic Matrix ◽

Bone Diseases ◽

Bone Collagen ◽

Type I ◽

New Therapeutic Approaches ◽

And Function

There is an increased interest and more studies highlight the fact that bone strength depends not only on bone tissue quantity, but also on its quality, which is characterized by the geometry and shape of bones, trabecular bone microarchitecture, mineral content, organic matrix and bone turnover. Fibrillar type I collagen is the major organic component of bone matrix, providing form and a stable template for mineralization. The biomedical importance of collagen as a biomaterial for medical and cosmetic purposes and the improvement of the molecular, cellular biology and analytical technologies, led to increasing interest in establishing the structure of this protein and in setting of the relationships between sequence, structure, and function. Bone collagen crosslinking chemistry and its molecular packing structure are considered to be distinct features. This unique post-translational modifications provide to the fibrillar collagen matrices properties such as tensile strength and viscoelasticity. Understanding the complex structure of bone type I collagen as well as the dynamic nature of bone tissues will help to manage new therapeutic approaches to bone diseases.

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Native cross-links in collagen fibrils induce resistance to human synovial collagenase

Biochemical Journal ◽

10.1042/bj1810639 ◽

1979 ◽

Vol 181 (3) ◽

pp. 639-645 ◽

Cited By ~ 150

Author(s):

C A Vater ◽

E D Harris ◽

R C Siegel

Keyword(s):

Lysyl Oxidase ◽

Collagen Fibrils ◽

Bone Collagen ◽

Collagen Molecule ◽

Cross Linking ◽

Pathological Conditions ◽

Insoluble Material ◽

Induce Resistance ◽

Cross Links

A model system consisting of highly purified lysyl oxidase and reconstituted lathyritic chick bone collagen fibrils was used to study the effect of collagen cross-linking on collagen degradation by mammalian collagenase. The results indicate that synthesis of approx. 0.1 Schiff-base cross-link per collagen molecule results in a 2–3-fold resistance to human synovial collagenase when compared with un-cross-linked controls or samples incubated in the presence of beta-aminopropionitrile to inhibit cross-linking. These results confirm previous studies utilizing artificially cross-linked collagens, or collagens isolated as insoluble material after cross-linking in vivo, and suggest that increased resistance to collagenase may be one of the earliest effects of cross-linking in vivo. The extent of intermolecular cross-linking among collagen fibrils may provide a mechanism for regulating the rate of collagen catabolism relative to synthesis in normal and pathological conditions.

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Bone matrix synthesis and mineralization of bone cells on hydroxylapatite-coated titanium surfaces

International Journal of Oral and Maxillofacial Surgery ◽

10.1016/s0901-5027(97)80020-3 ◽

1997 ◽

Vol 26 (6) ◽

pp. 467

Author(s):

H. Schliephake

Keyword(s):

Bone Cells ◽

Bone Matrix ◽

Matrix Synthesis ◽

Titanium Surfaces

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Collagen heterogeneity within different growth regions of long bones of rachitic and nonrachitic chicks

Biochemical Journal ◽

10.1042/bj1270715 ◽

1972 ◽

Vol 127 (4) ◽

pp. 715-720 ◽

Cited By ~ 86

Author(s):

Bryan P. Toole ◽

Andrew H. Kang ◽

Robert L. Trelstad ◽

Jerome Gross

Keyword(s):

Vitamin D ◽

Amino Acid ◽

Bone Matrix ◽

Bone Collagen ◽

Long Bone ◽

Long Bones ◽

Collagen Structure ◽

Collagen Molecules ◽

Relationship Of ◽

Chain Type

The different anatomical regions involved in osteogenesis in the chick long bone have been examined for heterogeneities in collagen structure that might relate to the mechanism of ossification. Experimentally induced lathyrism was employed to enhance collagen solubility, and vitamin D deficiency to allow accumulation of osteoid, the precursor of bone matrix. The extractable lathyritic collagens of the cartilaginous and osseous regions of growing long bones from rachitic and non-rachitic chicks were examined for α-chain type and amino acid composition. In both groups of animals the growth plate and cartilaginous regions of the epiphysis gave collagen molecules of the constitution [α1(II)]3, whereas the ossifying regions contained [α1(I)]2 α2. The degree of hydroxylation of the lysine moieties was increased by approximately 50% in the α1(I)-chain and α2-chain of rachitic bone collagen. Since uncalcified osteoid is greatly enriched in rachitic bone, it is concluded that the collagen of osteoid has the configuration [α1(I)]2 α2, similar to that of bone matrix, but has an elevated hydroxylysine content. The possible relationship of this difference to the mechanism of calcification is discussed.

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Integrin receptor-mediated mobilisation of intranuclear calcium in rat osteoclasts

Journal of Cell Science ◽

10.1242/jcs.105.1.61 ◽

1993 ◽

Vol 105 (1) ◽

pp. 61-68 ◽

Cited By ~ 2

Author(s):

G. Shankar ◽

I. Davison ◽

M.H. Helfrich ◽

W.T. Mason ◽

M.A. Horton

Keyword(s):

Cell Function ◽

Bone Cells ◽

Dynamic Equilibrium ◽

Bone Matrix ◽

Ion Concentration ◽

Calcium Signal ◽

Free Calcium ◽

Integrin Receptor ◽

Vitronectin Receptor ◽

Alpha V Beta 3

Cell-matrix interactions have been shown to play an important role in regulating cell function and behaviour. In bone, where calcified matrix formation and resorption events are required to be in dynamic equilibrium, regulation of adhesive interactions between bone cells and their matrix is critical. The present study focuses on the osteoclast, the bone resorbing cell, as well as integrins, which are cell surface adhesion receptors that mediate osteoclast attachment to bone matrix. In osteoclasts, the most abundant integrin receptor is the vitronectin receptor (VNR, alpha v beta 3). The objective of the study was to investigate changes in intracellular calcium, a regulator of osteoclast function, following addition of peptides that bind integrins, in particular the alpha v beta 3 form of the vitronectin receptor (VNR), which is highly expressed in osteoclasts. The study demonstrated a unique spatial localisation of the calcium signal in response to cell membrane receptor occupancy by integrin ligands in rat osteoclasts. Addition of peptides with the Arg-Gly-Asp (RGD) sequence such as BSP-IIA, GRGDSP and GRGDS to rat osteoclasts evoked an immediate increase in free calcium ion concentration [Ca2+]i, localised to the nuclei and to the thin cytoplasmic skirt. These responses were inhibited by F11, a monoclonal antibody to the rat integrin beta 3 chain, as well as echistatin, a snake venom shown to colocalise with the alpha v chain in osteoclasts, suggesting that the calcium signal is mediated by the alpha v beta 3 form of VNR.(ABSTRACT TRUNCATED AT 250 WORDS)

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Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation

Clinical Chemistry ◽

10.1093/clinchem/39.4.635 ◽

1993 ◽

Vol 39 (4) ◽

pp. 635-640 ◽

Cited By ~ 393

Author(s):

J Risteli ◽

I Elomaa ◽

S Niemi ◽

A Novamo ◽

L Risteli

Keyword(s):

Type I Collagen ◽

Polyacrylamide Gel Electrophoresis ◽

Sodium Dodecyl ◽

Bone Collagen ◽

Collagen Molecule ◽

Type I ◽

Serum Samples ◽

Amino Terminal ◽

Wide Range ◽

Carboxy Terminal

Abstract We developed a radioimmunoassay (RIA) for the carboxy-terminal telopeptides of type I collagen (ICTP), cross-linked with the helical domain of another type I collagen molecule, after isolation from human femoral bone. The cross-linked peptide was liberated by digesting insoluble, denatured bone collagen either with bacterial collagenase or with trypsin, and purified by two successive reversed-phase separations on HPLC, with monitoring of pyridinoline-specific fluorescence. The purity of the peptide was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its origin in the type I collagen fibers was determined by amino-terminal amino acid sequencing. Polyclonal antibodies and a separation reagent containing second antibody and polyethylene glycol are used in the RIA. An immunologically identical, somewhat larger antigen is present in human serum; its concentration increases in multiple myeloma and in rheumatoid arthritis. The ICTP antigen seems to be cleared from the circulation by the kidneys, because glomerular filtration rates that are two-thirds of normal or less are associated with increased circulating ICTP concentrations. The CVs of the method are between 3% and 8% for a wide range of concentrations. The analysis of 40 serum samples can be completed in 4 h.

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Calcium Efflux From Bone Matrix in Response to Mechanical Loading

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53625 ◽

2011 ◽

Author(s):

Xuanhao Sun ◽

Eric S. McLamore ◽

D. Marshall Porterfield ◽

Ozan Akkus

Keyword(s):

Hydrostatic Pressure ◽

Cell Surface ◽

Bone Cells ◽

Bone Matrix ◽

Mechanical Stimulus ◽

Calcium Efflux ◽

Fluid Shear ◽

Mechanical Environment ◽

Surface Receptors ◽

Cellular Events

Bone is known for its ability to self-repair the microdamage and actively adapt to its mechanical environment, both of which are under the coordination of bone cells. Mechanical cues are sensed by cells and converted into cellular events in a process called mechanotransduction [1]. Most theories of mechanotransduction are based on direct stimulus of cell surface receptors by substrate deformation, fluid shear and/or hydrostatic pressure [2]. Yet, mechanical stimulus may come to affect cell response indirectly, via pathways which alter the pericellular niche. Such indirect pathways of mechanotransduction are not well-investigated for bone.

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Mechanically Induced Calcium Release From Bone Matrix Triggers Intracellular Ca2+ Signalling in Osteoblasts: A Novel Mechanotransduction Mechanism

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53446 ◽

2011 ◽

Author(s):

Xuanhao Sun ◽

Vipuil Kishore ◽

Kateri Fites ◽

Ozan Akkus

Keyword(s):

Fluid Flow ◽

Hydrostatic Pressure ◽

Calcium Release ◽

Bone Cells ◽

Bone Matrix ◽

Bone Adaptation ◽

Exact Form ◽

Flow Shear ◽

Damage Repair ◽

Physical Stimuli

Bone cells are responsible for sensing and converting the mechanical signals into cellular signals to drive bone adaptation and damage repair [1]. Cell-mediated repair of bone is reported to be in preferential association with regions filled with microdamage [2]. Although different theories have been proposed for mechanisms involved in those processes (such as substrate deformation, fluid flow shear, and hydrostatic pressure in mechanotransduction [3], or microcrack and osteocyte apoptosis in damage detection [4]), knowledge on the exact form of physical stimuli which trigger bone cells, especially in critically loaded regions of bone, is still elusive.

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Intrafibrillar Mineralization of Collagen using a Liquid-Phase Mineral Precursor

MRS Proceedings ◽

10.1557/proc-774-o7.10 ◽

2003 ◽

Vol 774 ◽

Cited By ~ 5

Author(s):

Matthew J. Olszta ◽

Elliot P. Douglas ◽

Laurie B. Gower

Keyword(s):

Liquid Phase ◽

Material Science ◽

Type I Collagen ◽

Collagen Matrix ◽

Collagen Fibrils ◽

Type I ◽

Mineral Phase ◽

Capillary Action ◽

Acid Etch ◽

Mineralized Collagen

AbstractIntrafibrillar mineralization of type-I collagen with hydroxyapatite (HA) is the basis of the complex biological composite known as bone, which from a material science perspective is a fascinating example of an interpenetrating bioceramic composite. Using a polymer-induced liquid-precursor (PILP) process, collagen substrates were highly infiltrated with a liquid-phase mineral precursor to calcium carbonate (CaCO3). At sections of partially mineralized collagen, banded mineral patterns were observed perpendicular to the collagen fibrils, while other fibrils were completely mineralized. An acid etch, used to preferentially remove superficial mineral, further revealed such banded patterns in fully mineralized samples. Removal of the collagen matrix with a dilute hypochlorite solution showed an interpenetrating mineral phase, with mineral disks that spanned the diameter of the pre-existing collagen fibrils, supporting our hypothesis that intrafibrillar mineralization can be achieved via capillary action applied to a liquid-phase mineral precursor.

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