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Results for “COLLAGEN”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
NASA NTRS1990

Collagen in the spicule organic matrix of the gorgonian Leptogorgia virgulata

Decalcification of the calcareous spicules from the gorgonian Leptogorgia virgulata reveals an organic matrix that may be divided into water insoluble and soluble fractions. The insoluble fraction displays characteristics typical of collagen, which is an unusual component of an invertebrate calcium carbonate structure. This matrix fraction exhibits a collagenous amino acid profile and behavior upon SDS-PAGE. Furthermore, the reducible crosslink, dihydroxylysinonorleucine (DHLNL), is detected in this fraction. The composition of the matrix varies seasonally; i.e., the collagenous composition is most prevalent in the summer. These results indicate that the insoluble matrix is a dynamic structure. Potential roles of this matrix in spicule calcification are discussed.

Non-NASA Center↗
NASA NTRS1999

Persistence of bone collagen cross-links in skeletons of the Nuraghi population living in Sardinia 1500-1200 B.C

Bone collagen has a specific molecular ultrastructure which can be proved by birefringence. This protein, forming the main organic component of bone tissue, is known to survive millennia in paleontological bones and teeth. Birefringence of bone collagen obtained from the skeletons of the Nuraghi population living in Sardinia c-ca 1500 years B.C. was found previously by the use of polarizing microscopy [1]. In this paper, using high pressure liquid chromatography (HPLC) techniques, we show the existence of bone collagen cross-links preserved in Nuraghi skeletons after more than 3000 years.

Non-NASA Center↗
NASA NTRS1997

Alteration of mineral crystallinity and collagen cross-linking of bones in osteopetrotic toothless (tl/tl) rats and their improvement after treatment with colony stimulating factor-1

A common feature of various types of mammalian osteopetroses is a marked increase in bone mass accompanied by spontaneous bone fractures. The toothless (tl/tl) rat osteopetrotic mutation is characterized by drastically reduced bone resorption due to a profound deficiency of osteoclasts and their precursors. An altered bone morphology has also been observed. The mutants cannot be cured by bone marrow transplantation, but skeletal defects are greatly reduced after treatment with colony stimulating factor 1 (CSF-1). The objectives of this study were to characterize mineral and collagen matrices in cancellous and compact bone isolated from long bones of 6-week-old normal littermates, tl/tl osteopetrotic mutants and mutants (tl/tl) treated with CSF-1. There were no differences in bone mineral content, but a significant decrease in the crystallinity of mineral evaluated by the method based on electron paramagnetic resonance spectrometry was observed in all bones of tl/tl mutants as compared to that of controls. Within the collagen matrix, slight decreases in the labile cross-links, but significant increases in the content of the stable cross-links, pyridinoline, and deoxypyridinoline, were observed in both cancellous and compact bone of osteopetrotic mutants. In tl/tl mutants treated with human recombinant CSF-1, the normalization of the crystallinity of bone mineral as well as collagen cross-links was found. Our results indicate that remodeling of bone matrix in tl/tl mutants is highly suppressed, but that after treatment with CSF-1, this activity recovers significantly. Taken together, these data provide further support for the hypothesis that CSF-1 is an essential factor for normal osteoclast differentiation and bone remodelling.

NASA Discipline Musculoskeletal↗
DOE OSTI2022

Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation

ABSTRACT Diabetes mellitus (DM) is an emerging metabolic disease, and the management of diabetic bone disease poses a serious challenge worldwide. Understanding the underlying mechanisms leading to high fracture risk in DM is hence of particular interest and urgently needed to allow for diagnosis and treatment optimization. In a case–control postmortem study, the whole 12th thoracic vertebra and cortical bone from the mid-diaphysis of the femur from male individuals with type 1 diabetes mellitus (T1DM) (n = 6; 61.3 ± 14.6 years), type 2 diabetes mellitus (T2DM) (n = 11; 74.3 ± 7.9 years), and nondiabetic controls (n = 18; 69.3 ± 11.5) were analyzed with clinical and ex situ imaging techniques to explore various bone quality indices. Cortical collagen fibril deformation was measured in a synchrotron setup to assess changes at the nanoscale during tensile testing until failure. In addition, matrix composition was analyzed including determination of cross-linking and non-crosslinking advanced glycation end-products like pentosidine and carboxymethyl-lysine. In T1DM, lower fibril deformation was accompanied by lower mineralization and more mature crystalline apatite. In T2DM, lower fibril deformation concurred with a lower elastic modulus and tendency to higher accumulation of non-crosslinking advanced glycation end-products. The observed lower collagen fibril deformation in diabetic bone may be linked to altered patterns mineral characteristics in T1DM and higher advanced glycation end-product accumulation in T2DM. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Collagen Fibril Orientation in Tissue Specimens From Atherosclerotic Plaque Explored Using Small Angle X-Ray Scattering

Atherosclerotic plaques can gradually develop in certain arteries. Disruption of fibrous tissue in plaques can result in plaque rupture and thromboembolism, leading to heart attacks and strokes. Collagen fibrils are important tissue building blocks and tissue strength depends on how fibrils are oriented. Fibril orientation in plaque tissue may potentially influence vulnerability to disruption. While X-ray scattering has previously been used to characterize fibril orientations in soft tissues and bones, it has never been used for characterization of human atherosclerotic plaque tissue. This study served to explore fibril orientation in specimens from human plaques using small angle X-ray scattering (SAXS). Additionally, plaque tissue was extracted from human femoral and carotid arteries, and each tissue specimen contained a region of calcified material. Three-dimensional (3D) collagen fibril orientation was determined along scan lines that started away from and then extended toward a given calcification. Fibrils were found to be oriented mainly in the circumferential direction of the plaque tissue at the majority of locations away from calcifications. However, in a number of cases, the dominant fibril direction differed near a calcification, changing from circumferential to longitudinal or thickness (radial) directions. Further study is needed to elucidate how these fibril orientations may influence plaque tissue stress–strain behavior and vulnerability to rupture.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2003

Inhibition of HSP70 and a Collagen-Specific Molecular Chaperone (HSP47) Expression in Rat Osteoblasts by Microgravity

Rat osteoblasts were cultured aboard a space shuttle for 4 or 5 days. Cells were exposed to 1alpha, 25 dihydroxyvitamin D(3) during the last 20 h and then solubilized by guanidine solution. The mRNA levels for molecular chaperones were analyzed by semi-quantitative RT-PCR. ELISA was used to quantify TGF-beta1 in the conditioned medium. The HSP70 mRNA levels in the flight cultures were almost completely suppressed, as compared to the ground (1 x g) controls. The inducible HSP70 is known as the major heat shock protein that prevents stress-induced apoptosis. The mean mRNA levels for the constitutive HSC73 in the flight cultures were reduced to 69%, approximately 60% of the ground controls. HSC73 is reported to prevent the pathological state that is induced by disruption of microtubule network. The mean HSP47 mRNA levels in the flight cultures were decreased to 50% and 19% of the ground controls on the 4th and 5th days. Concomitantly, the concentration of TGF-beta1 in the conditioned medium of the flight cultures was reduced to 37% and 19% of the ground controls on the 4th and 5th days. HSP47 is the collagen-specific molecular chaperone that controls collagen processing and quality and is regulated by TGF-beta1. Microgravity differentially modulated the expression of molecular chaperones in osteoblasts, which might be involved in induction and/or prevention of osteopenia in space.

Animals↗
DOE OSTI2024

Aging impairs the osteocytic regulation of collagen integrity and bone quality

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβ signaling (TβRII ocy–/– ) that suppresses PLR. The control aged bone displayed decreased TGFβ signaling and PLR, but aging did not worsen the existing PLR suppression in male TβRII ocy–/– bone. This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFβ. We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Mesoporous peptide frameworks engineered from crystallizable collagen-mimetic peptide amphiphiles

The rational design of porous frameworks with tunable pore dimensions and chemical functionalities is a critical step toward their implementation in diverse applications. While traditional porous materials are typically constructed from abiotic components, there is increasing interest in employing biologically derived building blocks (e.g., peptides and proteins) that offer unmatched structural and functional diversity. Here, we report the construction of crystalline mesoporous frameworks that are self-assembled from amphiphilic collagen-mimetic peptides. Comprehensive structural characterization via microscopy, spectroscopy, and computational techniques provides insights into the assembly packing model, in which hexagonally packed channels are interconnected by antiparallel-aligned collagen triple helices via hydrophobic and electrostatic interactions. Lastly, we demonstrate the functional potential of aCMP frameworks through the encapsulation of various molecular guests, including doxorubicin, an anti-cancer drug. Overall, this work establishes a class of mesoporous frameworks, derived from synthetically engineerable peptide conjugates, marking a significant step forward in broadening the architectural scope and application potential of peptide-based materials.

Perez, Anthony R↗
NASA NTRS1996

Collagen Gel Contraction by Fibroblasts: The Role of Myosin 2 and Gravity Effects

Several lines of evidence suggest that collagen organization by connective tissue cells is sensitive to force. For instance, in flight experiments on rats the collagen fibrils which were produced under weightlessness and which were immediately next to the tendon fibroblasts were shown to be oriented randomly around the cells while the older fibrils right next to these and which were produced under 1 G, were highly organized.

Johnson-Wint, Barbara P.↗
NASA NTRS1997

The Structure and Function of Non-Collagenous Bone Proteins

The research done under the cooperative research agreement for the project titled 'The structure and function of non-collagenous bone proteins' represented the first phase of an ongoing program to define the structural and functional relationships of the principal noncollagenous proteins in bone. An ultimate goal of this research is to enable design and execution of useful pharmacological compounds that will have a beneficial effect in treatment of osteoporosis, both land-based and induced by long-duration space travel. The goals of the now complete first phase were as follows: 1. Establish and/or develop powerful recombinant protein expression systems; 2. Develop and refine isolation and purification of recombinant proteins; 3. Express wild-type non-collagenous bone proteins; 4. Express site-specific mutant proteins and domains of wild-type proteins to enhance likelihood of crystal formation for subsequent solution of structure.

Hook, Magnus↗
NASA NTRS1992

Collagen in organ development

It is important to know whether microgravity will adversely affect developmental processes. Collagens are macromolecular structural components of the extracellular matrix (ECM) which may be altered by perturbations in gravity. Interstitial collagens have been shown to be necessary for normal growth and morphogenesis in some embryonic organs, and in the mouse salivary gland, the biosynthetic pattern of these molecules changes during development. Determination of the effects of microgravity on epithelial organ development must be preceded by crucial ground-based studies. These will define control of normal synthesis, secretion, and deposition of ECM macromolecules and the relationship of these processes to morphogenesis.

NASA Discipline Cell Biology↗
NASA NTRS1998

Collagen cross-link excretion during space flight and bed rest

Extended exposure to weightlessness results in bone loss. However, little information exists as to the precise nature or time course of this bone loss. Bone resorption results in the release of collagen breakdown products, including N-telopeptide and the pyridinium (PYD) cross-links, pyridinoline and deoxypyridinoline. Urinary pyridinoline and deoxypyridinoline are known to increase during bed rest. We assessed excretion of PYD cross-links and N-telopeptide before, during, and after long (28-day, 59-day, and 84-day) Skylab missions, as well as during short (14-day) and long (119-day) bed-rest studies. During space flight, the urinary cross-link excretion level was twice those observed before flight. Urinary excretion levels of the collagen breakdown products were also 40-50% higher, during short and long bed rest, than before. These results clearly show that the changes in bone metabolism associated with space flight involve increased resorption. The rate of response (i.e. within days to weeks) suggests that alterations in bone metabolism are an early effect of weightlessness. These studies are important for a better understanding of bone metabolism in space crews and in those who are bedridden.

NASA Center JSC↗
NASA NTRS2004

Modeled Microgravity Disrupts Collagen I/Integrin Signaling During Osteoblastic Differentiation of Human Mesenchymal Stem Cells

Spaceflight leads to reduced bone mineral density in weight bearing bones that is primarily attributed to a reduction in bone formation. We have previously demonstrated severely reduced osteoblastogenesis of human mesenchymal stem cells (hMSC) following seven days culture in modeled microgravity. One potential mechanism for reduced osteoblastic differentiation is disruption of type I collagen-integrin interactions and reduced integrin signaling. Integrins are heterodimeric transmembrane receptors that bind extracellular matrix proteins and produce signals essential for proper cellular function, survival, and differentiation. Therefore, we investigated the effects of modeled microgravity on integrin expression and function in hMSC. We demonstrate that seven days of culture in modeled microgravity leads to reduced expression of the extracellular matrix protein, type I collagen (Col I). Conversely, modeled microgravity consistently increases Col I-specific alpha2 and beta1 integrin protein expression. Despite this increase in integrin sub-unit expression, autophosphorylation of adhesion-dependent kinases, focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2), is significantly reduced. Activation of Akt is unaffected by the reduction in FAK activation. However, reduced downstream signaling via the Ras-MAPK pathway is evidenced by a reduction in Ras and ERK activation. Taken together, our findings indicate that modeled microgravity decreases integrin/MAPK signaling, which likely contributes to the observed reduction in osteoblastogenesis.

Meyers, Valerie E.↗
NASA NTRS2018

Ionizing Radiation from Ex Vivo Sterilization Diminishes Collagen Integrity and Vertebral Body Mechanics

Clinical exposure to ionizing radiation could put cancer radiotherapy or bone allograft patients at an increased risk of fracture. In these applications, ionizing radiation levels can range from accumulative 50 Gy for radiotherapy cancer treatment, to acute 35,000 Gy for allograft sterilization. Ionizing radiation has been shown to decrease bon equality through reduced strength and post-yield properties and degrade collagen integrity through either increased crosslinks (advanced glycation end products, AGEs)or fragmentation. It is unclear which collagen structural change accounts for reduced strength. The dose-dependent effect of ionizing radiation on mechanical and biochemical properties of whole bones are not well understood, particularly for ex vivo doses ranging from 50 to 35,000 Gy.

Radiation↗
NASA NTRS2022

Latex–collagen membrane: an alternative treatment for tibial bone defects

Due to the difficulty of consolidation, the risk of fractures, and the high cost of therapy, the orthopedic field views the restoration of bony defects or post-traumatic diseases as a significant issue. In recent years, efforts have been made toward guided bone regeneration as a viable solution. In this study, natural rubber latex (NRL) and latex–collagen (NRL-COL) membranes were developed and characterized, and their effects on bone regeneration in rat tibial lesions were assessed. According to the physicochemical findings, the hydrolyzed COL was effectively incorporated into the NRL membrane to produce a more robust membrane (348% increase in stress) and showed good biocompatibility for human dermal fibroblast cells and in hemolytic activity assay. According to bone analysis using computed microtomography, a substantial difference in bone volume (BV) was found among NRL, control (CONT), and NRL-COL. NRL-COL exhibited the greatest value for the bone volume/total volume ratio (BV/TV). The presence of NRL and COL was significant for the analysis of BV and BV/TV, respectively. All the experimental groups demonstrated a higher bone quality and fracture resistance, as shown by the mechanical properties of the bone. In the COL group, both neoformation of bone and total collagen levels were greater, indicating that treated defects had been closed and mature bone cells were present. Due to its angiogenic properties and the low cost of NRL membrane production, the NRL-COL membrane could be a good substitute for upcoming bone regeneration applications.

Marcela Britto de Paiva↗
DOE OSTI2021

Radiation Toxicity in Patients With Collagen Vascular Disease: A Meta-Analysis of Case-Control Studies

Several retrospective series have reported that patients with collagen vascular disease (CVD) are at increased risk of radiation (RT) toxicity. However, the evidence is mixed, and many series lack control groups. We performed a meta-analysis including only case-cohort or randomized studies that examined the risk of RT toxicity for patients with CVD compared with controls.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2026

Structural and Mechanical Analysis of Individual Mineralized Collagen Fibrils Using In Situ Transmission Electron Microscopy

Bone serves as an example of nature’s architectured material with its characteristic blend of strength and toughness, all at a lightweight design. Given the hierarchical nature of these materials, it is essential to understand the governing mechanisms and organization of their constituents across length scales for bioinspired structural design. Despite recent advances in transmission electron microscopy (TEM) that have allowed us to witness the hierarchical arrangement of bone at micro-down to the nanoscale, we are still missing the details about the structural organization and mechanical properties of the main building blocks of bone─mineralized collagen fibrils (MCFs). Here, we present a method to extract individual MCFs from nature’s model material, mineralized turkey leg tendon, using a dropcasting procedure. By isolating the MCFs onto TEM supporting grids, we visualized the arrangement of organic and mineral phases within individual MCFs at the nanoscale. Using a four-dimensional scanning transmission electron microscopy (4D-STEM) approach, the orientation of individual mineral crystals within the MCFs was examined. Furthermore, we conducted in situ tensile experiments, revealing exceptional tensile strains of at least 8%, demonstrating the intricate relationship between structural organization and the mechanical behavior of MCFs. These insights into the ultrastructure of mineralized tissue building blocks, as well as the proposed sample-extraction method compatible with in situ mechanical testing, provide a strong basis for research into nature-inspired material design.

4D-STEM↗