scholarly journals Deciphering the Relevance of Bone ECM Signaling

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2630
Author(s):  
Natividad Alcorta-Sevillano ◽  
Iratxe Macías ◽  
Arantza Infante ◽  
Clara I. Rodríguez
Keyword(s):  
Bone Matrix ◽  
Three Dimensional ◽  
Collagen Type I ◽  
Bone Fragility ◽  
Dimensional Structure ◽  
Type I ◽  
Mineral Density ◽  
Noncollagenous Proteins ◽  
Ecm Proteins ◽  
Inorganic And Organic

Bone mineral density, a bone matrix parameter frequently used to predict fracture risk, is not the only one to affect bone fragility. Other factors, including the extracellular matrix (ECM) composition and microarchitecture, are of paramount relevance in this process. The bone ECM is a noncellular three-dimensional structure secreted by cells into the extracellular space, which comprises inorganic and organic compounds. The main inorganic components of the ECM are calcium-deficient apatite and trace elements, while the organic ECM consists of collagen type I and noncollagenous proteins. Bone ECM dynamically interacts with osteoblasts and osteoclasts to regulate the formation of new bone during regeneration. Thus, the composition and structure of inorganic and organic bone matrix may directly affect bone quality. Moreover, proteins that compose ECM, beyond their structural role have other crucial biological functions, thanks to their ability to bind multiple interacting partners like other ECM proteins, growth factors, signal receptors and adhesion molecules. Thus, ECM proteins provide a complex network of biochemical and physiological signals. Herein, we summarize different ECM factors that are essential to bone strength besides, discussing how these parameters are altered in pathological conditions related with bone fragility.

scholarly journals Recruitment of osteoclast precursors by purified bone matrix constituents.

1982 ◽  
Vol 92 (1) ◽  
pp. 227-230 ◽  
Author(s):  
J D Malone ◽  
S L Teitelbaum ◽  
G L Griffin ◽  
R M Senior ◽  
A J Kahn
Keyword(s):  
Type I Collagen ◽  
Human Peripheral Blood ◽  
Bone Matrix ◽  
Chemotactic Response ◽  
Type I ◽  
Polymorphonuclear Leucocytes ◽  
Blood Monocytes ◽  
Noncollagenous Proteins ◽  
Osteoclast Precursors ◽  
Collagen Peptides

The osteoclast, the multinucleated giant cell of bone, is derived from circulating blood cells, most likely monocytes. Evidence has accrued that is consistent with the hypothesis that the recruitment of monocytes for osteoclast development occurs by chemotaxis. In the present study, we have examined the chemotactic response of human peripheral blood monocytes and related polymorphonuclear leucocytes to three constituents of bone matrix: peptides from Type I collagen, alpha 2-HS glycoprotein, and osteocalcin (bone gla protein). The latter two substances are among the major noncollagenous proteins of bone and are uniquely associated with calcified connective tissue. In chemotaxis assays using modified Boyden chambers, Type I collagen peptides, alpha 2HS glycoprotein, and osteocalcin evoke a dose-dependent chemotactic response in human monocytes. No chemotaxis is observed on PMNs despite their ontogenetic relationship to monocytes and their documented sensitivity to a broad range of other chemical substances. Our observations are consistent with the view that osteoclast precursors (monocytes) are mobilized by chemotaxis, and suggest that the chemoattractants responsible for this activity are derived from the bone matrix or, in the case of collagen and osteocalcin; directly from the osteoblasts which produce them.

Collagen Expression in Tissue Engineered Cartilage of Aged Human Articular Chondrocytes in a Rotating Bioreactor

2003 ◽  
Vol 26 (4) ◽  
pp. 319-330 ◽  
Author(s):  
S. Marlovits ◽  
B. Tichy ◽  
M. Truppe ◽  
D. Gruber ◽  
W. Schlegel
Keyword(s):  
Electron Microscopy ◽  
Collagen Type ◽  
Articular Chondrocytes ◽  
Three Dimensional ◽  
Collagen Type I ◽  
Human Articular Chondrocytes ◽  
Type I ◽  
Transmission Electron ◽  
Low Shear Stress ◽  
Engineered Cartilage

This study describes the culture and three-dimensional assembly of aged human articular chondrocytes under controlled oxygenation and low shear stress in a rotating-wall vessel. Chondrocytes cultured in monolayer were released and placed without any scaffold as a single cell suspension in a rotating bioreactor for 12 weeks. Samples were analyzed with immunohistochemistry, molecular biology and electron microscopy. During serial monolayer cultures chondrocytes dedifferentiated to a “fibroblast-like” structure and produced predominantly collagen type I. When these dedifferentiated cells were transferred to the rotating bioreactor, the cells showed a spontaneous aggregation and formation of solid tissue during the culture time. Expression of collagen type II and other components critical for the extracellular cartilage matrix could be detected. Transmission electron microscopy revealed a fine network of randomly distributed collagen fibrils. This rotating bioreactor proves to be a useful tool for providing an environment that enables dedifferentiated chondrocytes to redifferentiate and produce a cartilage-specific extracellular matrix.

scholarly journals The effects of discontinuing long term alendronate therapy in a clinical practice setting

2011 ◽  
Vol 55 (4) ◽  
pp. 272-278 ◽  
Author(s):  
André Gonçalves da Silva ◽  
José Gilberto H. Vieira ◽  
Ilda Sizue Kunii ◽  
Janaína Martins de Lana ◽  
Marise Lazaretti-Castro
Keyword(s):  
Bone Turnover ◽  
Collagen Type I ◽  
Type I ◽  
Mineral Density ◽  
Procollagen Type ◽  
Post Menopausal Osteoporosis ◽  
Treatment Naïve ◽  
Turnover Markers ◽  
Group 2 ◽  
Post Menopausal

OBJECTIVE: To assess bone turnover markers (BTM) and bone mineral density (BMD) after discontinuation of alendronate treatment used for five or more years. SUBJECTS AND METHODS: 40 patients (pt) with post-menopausal osteoporosis treated with alendronate (10 mg/d) for at least five years (Group 1, G1) had their medication discontinued. Group 2 (G2): 25 pt treated with alendronate for at least one year. Group 3 (G3): 23 treatment-naïve osteoporotic pt. BMD was evaluated in G1 and G2 at baseline and after 12 months. Collagen type I cross-linked C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels were measured in all pt at baseline, and in G1 and G2 every three months for 12 months. Data were analyzed using ANOVA on ranks and Mann-Whitney tests. RESULTS: Mean BMD values in G1 and G2 did not differ during follow-up. However, 16 pt (45.7%) in G1 and one (5.2%) in G2 lost BMD (P < 0.001). BTM at baseline was not different between G1 and G2, and both were lower than G3. A significant increase in BTM levels was detected in G1 pt after three months, but not in G2. CONCLUSION: Observed BMD loss and BTM rise after alendronate withdrawal imply that bone turnover was not over suppressed, and alendronate discontinuation may not be safe.

Mesenchymal stem cells from adipose tissue which have been differentiated into chondrocytes in three-dimensional culture express lubricin

2011 ◽  
Vol 236 (11) ◽  
pp. 1333-1341 ◽  
Author(s):  
Giuseppe Musumeci ◽  
Debora Lo Furno ◽  
Carla Loreto ◽  
Rosario Giuffrida ◽  
Silvia Caggia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Collagen Type ◽  
Three Dimensional ◽  
3D Culture ◽  
Collagen Type I ◽  
Type I ◽  
Human Mscs ◽  
Alternative Source

The present study focused on the isolation, cultivation and characterization of human mesenchymal stem cells (MSCs) from adipose tissue and on their differentiation into chondrocytes through the NH ChondroDiff medium. The main aim was to investigate some markers of biomechanical quality of cartilage, such as lubricin, and collagen type I and II. Little is known, in fact, about the ability of chondrocytes from human MSCs of adipose tissue to generate lubricin in three-dimensional (3D) culture. Lubricin, a 227.5-kDa mucinous glycoprotein, is known to play an important role in articular joint physiology, and the loss of accumulation of lubricin is thought to play a role in the pathology of osteoarthritis. Adipose tissue is an alternative source for the isolation of multipotent MSCs, which allows them to be obtained by a less invasive method and in larger quantities than from other sources. These cells can be isolated from cosmetic liposuctions in large numbers and easily grown under standard tissue culture conditions. 3D chondrocytes were assessed by histology (hematoxylin and eosin) and histochemistry (Alcian blue and Safranin-O/fast green staining). Collagen type I, II and lubricin expression was determined through immunohistochemistry and Western blot. The results showed that, compared with control cartilage and monolayer chondrocytes showing just collagen type I, chondrocytes from MSCs (CD44-, CD90- and CD105- positive; CD45-, CD14- and CD34-negative) of adipose tissue grown in nodules were able to express lubricin, and collagen type I and II, indicative of hyaline cartilage formation. Based on the function of lubricin in the joint cavity and disease and as a potential therapeutic agent, our results suggest that MSCs from adipose tissue are a promising cell source for tissue engineering of cartilage. Our results suggest that chondrocyte nodules producing lubricin could be a novel biotherapeutic approach for the treatment of cartilage abnormalities.

scholarly journals Preliminary Study of In Vitro Three-Dimensional Skin Model Using an Ovine Collagen Type I Sponge Seeded with Co-Culture Skin Cells: Submerged versus Air-Liquid Interface Conditions

Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 2784
Author(s):  
Mh Busra Fauzi ◽  
Zahra Rashidbenam ◽  
Aminuddin Bin Saim ◽  
Ruszymah Binti Hj Idrus
Keyword(s):  
Collagen Type ◽  
Three Dimensional ◽  
Collagen Type I ◽  
Liquid Interface ◽  
Type I ◽  
Skin Model ◽  
Skin Cells ◽  
Air Liquid Interface ◽  
In Vitro Skin Model

Three-dimensional (3D) in vitro skin models have been widely used for cosmeceutical and pharmaceutical applications aiming to reduce animal use in experiment. This study investigate capability of ovine tendon collagen type I (OTC-I) sponge suitable platform for a 3D in vitro skin model using co-cultured skin cells (CC) containing human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF) under submerged (SM) and air-liquid interface (ALI) conditions. Briefly, the extracted OTC-I was freeze-dried and crosslinked with genipin (OTC-I_GNP) and carbodiimide (OTC-I_EDC). The gross appearance, physico-chemical characteristics, biocompatibility and growth profile of seeded skin cells were assessed. The light brown and white appearance for the OTC-I_GNP scaffold and other groups were observed, respectively. The OTC-I_GNP scaffold demonstrated the highest swelling ratio (~1885%) and water uptake (94.96 ± 0.14%). The Fourier transformation infrared demonstrated amide A, B and I, II and III which represent collagen type I. The microstructure of all fabricated sponges presented a similar surface roughness with the presence of visible collagen fibers and a heterogenous porous structure. The OTC-I_EDC scaffold was more toxic and showed the lowest cell attachment and proliferation as compared to other groups. The micrographic evaluation revealed that CC potentially formed the epidermal- and dermal-like layers in both SM and ALI that prominently observed with OTC-I_GNP compared to others. In conclusion, these results suggest that OTC_GNP could be used as a 3D in vitro skin model under ALI microenvironment.

scholarly journals Altered affinity of insulin-like growth factor II (IGF-II) for receptors and IGF-binding proteins, resulting from limited modifications of the IGF-II molecule

1991 ◽  
Vol 278 (1) ◽  
pp. 249-254 ◽  
Author(s):  
Y Oh ◽  
M W Beukers ◽  
H M Pham ◽  
P A Smanik ◽  
M C Smith ◽  
...  
Keyword(s):  
Amino Acids ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Type I ◽  
Type Ii ◽  
Factor Ii ◽  
N Terminus ◽  
Severe Impairment ◽  
Igf Binding ◽  
Terminal Amino

The binding affinities of seven analogues of recombinant human insulin-like growth factor II (hIGF-II) were characterized for the IGF type-I and type-II receptors and insulin receptors, as well as for IGF-binding protein (IGFBP)-1, IGFBP-2, IGFPB-3 and human serum IGFBPs. A switch of two of the three cysteine bridges in hIGF-II, 9-47 and 46-51 to 9-46 and 47-51, severely impaired the binding of this analogue to all receptors and to the IGFBPs. The affinities for the IGF type-I receptor and the IGFBPs were decreased over 100-fold, while the binding to the insulin receptor and the IGF type-II receptor was less affected, with a 6-10-fold decrease in affinity. Slight modifications of the N-terminus had only minor effects upon the binding of hIGF-II to the IGFBPs or to the receptors. Deletion of both the N-terminal amino acid and the two C-terminal amino acids resulted in moderate decreases in affinity, with a 60% decrease in affinity for IGFBP-1 and the IGF type-I receptor. Acetylation of the N-terminus of Ala1 and the epsilon-nitrogen of Lys65 decreased the affinity, by 60-90%, of hIGF-II for all of the IGFBPs and receptors. The experiments involving acetylation of IGF-II or switching of its cysteine bridges indicated that these modifications (no substitution, deletion or addition of any of the 67 amino acids of hIGF-II) may lead to a severe impairment of the binding affinity of IGF-II for both the IGFBPs and the receptors. Acetylation of the epsilon-nitrogen of Lys65, which causes a charge change, or alteration of the three-dimensional structure, as shown by the cysteine bridge switch, lead to a severe impairment of the binding affinity for the binding proteins and for the receptors. In general, care should be taken with the synthesis of analogues and the interpretation of resulting binding data, since affinity alterations ascribed to amino acid changes may instead be caused by alterations of the charge or the three-dimensional structure of the protein.

Type I interferon structures: Possible scaffolds for the interferon-alpha receptor complex

2002 ◽  
Vol 80 (8) ◽  
pp. 1166-1173 ◽  
Author(s):  
Tattanahalli L Nagabhushan ◽  
Paul Reichert ◽  
Mark R Walter ◽  
Nicholas J Murgolo
Keyword(s):  
Structural Model ◽  
Structural Information ◽  
Three Dimensional ◽  
Cell Receptor ◽  
Type I Interferons ◽  
Dimensional Structure ◽  
Type I ◽  
Receptor Complex ◽  
X Ray Crystallography ◽  
Receptor Complexes

The structures of several type I interferons (IFNs) are known. We review the structural information known for IFN alphas and compare them to other interferons and cytokines. We also review the structural information known or proposed for IFN–cell receptor complexes. However, the structure of the IFN – cell receptor – IFN receptor2 (IFNAR2) and IFN receptor1 (IFNAR1) complex has not yet been determined. This paper describes a structural model of human IFN-IFNAR2/IFNAR1 complex using human IFN-α2b dimer as the ligand. Both the structures of recombinant human IFN-α2b and IFN-β were determined by X-ray crystallography as zinc-mediated dimers. Our proposed model was generated using human IFN-α2b dimer docked with IFNAR2/IFNAR1. We compare our model with the receptor complex models proposed for IFN-β and IFN-γ to contrast similarities and differences. The mutual binding sites of human IFN-α2b and IFNAR2/IFNAR1 complex are consistent with available mutagenesis studies.Key words: three dimensional structure, antiviral activity, receptor, interferon.

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