scholarly journals Mechanisms balancing skeletal matrix synthesis and degradation

2002 ◽  
Vol 364 (2) ◽  
pp. 329-341 ◽  
Author(s):  
Harry C. BLAIR ◽  
Mone ZAIDI ◽  
Paul H. SCHLESINGER
Keyword(s):  
Parathyroid Hormone ◽  
Type I Collagen ◽  
Bone Matrix ◽  
Type Ii Collagen ◽  
Type I ◽  
Parathyroid Hormone Related Protein ◽  
Bone Degradation ◽  
The Matrix ◽  
Acid Secreting ◽  
Matrix Removal

Bone is regulated by evolutionarily conserved signals that balance continuous differentiation of bone matrix-producing cells against apoptosis and matrix removal. This is continued from embryogenesis, where the skeleton differentiates as a solid mass and is shaped into separate bones by cell death and proteolysis. The two major tissues of the skeleton are avascular cartilage, with an extracellular matrix based on type II collagen and hydrophilic proteoglycans, and bone, a stronger and lighter material based on oriented type I collagen and hydroxyapatite. Both differentiate from the same mesenchymal stem cells. This differentiation is regulated by a family of related signals centred on bone morphogenic proteins. Fibroblast growth factors, Indian hedgehog and parathyroid hormone-related protein are important in determining the type of matrix and the relation of skeletal and non-skeletal structures. Removal of mineralized matrix involves apoptosis of matrix cells and differentiation of acid-secreting cells (osteoclasts) from macrophage precursors. Key regulators of matrix removal are signals in the tumour-necrosis-factor family. Osteoclasts dissolve bone by isolating a region of the matrix and secreting HCl and proteinases at that site. Successive cycles of removal and replacement allow growth, repair and remodelling. The signals for bone turnover are predominantly cell-membrane-associated, allowing very specific spatial regulation. In addition to its support function, bone is a reservoir of Ca2+, PO3-4 and OH−. Secondary modulation of mineral secretion and bone degradation are mediated by humoral signals, including parathyroid hormone and vitamin D, as well as the cytokines that also regulate the underlying cell differentiation.

Carboxyterminal telopeptide of type I collagen, ICTP, as a marker of matrix degradation in neonatal mouse calvarial bones, in vitro

1992 ◽  
Vol 12 (5) ◽  
pp. 407-411 ◽  
Author(s):  
Östen Ljunggren ◽  
Sverker Ljunghall
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Type I Collagen ◽  
Bone Matrix ◽  
Neonatal Mouse ◽  
Type I ◽  
Matrix Degradation ◽  
Dose Responses ◽  
Carboxyterminal Telopeptide

Bone resorption, in vitro, is often measured as the release of prelabelled45Ca from neonatal mouse calvarial bones, or from fetal rat long bones. In this report we describe a technique to measure the breakdown of bone-matrix, in vitro. We also describe a new way to dissect neonatal mouse calvarial bones, in order to obtain large amounts of bone samples. Twelve bone fragments were dissected out from each mouse calvaria and were thereafter cultured in CMRL 1066 culture medium in serum-free conditions in 0.5 cm2 multiwell culture dishes. Matrix degradation after treatment with parathyroid hormone was assessed by measuring the amount of carboxyterminal telopeptide of type I collagen (ICTP) by RIA. The data on matrix degradation was compared to the release of prelabelled45Ca from neonatal mouse calvarial bones. We found that the dose-responses for parathyroid hormone-induced release of prelabelled45Ca and ICTP were identical. In conclusion: RIA-analysis of the ICTP-release is an easy and accurate method to measure degradation of bone-matrix, in vitro. Furthermore, the new dissection technique, described in this report, makes it easy to obtain large amounts of bone samples and thus to perform extensive experiments, e.g. dose-responses for agents that enhance bone resorption.

scholarly journals Control of Bone Matrix Properties by Osteocytes

2021 ◽  
Vol 11 ◽  
Author(s):  
Amy Creecy ◽  
John G. Damrath ◽  
Joseph M. Wallace
Keyword(s):  
Type I Collagen ◽  
Bone Matrix ◽  
Type I ◽  
Bone Homeostasis ◽  
Surrounding Matrix ◽  
Matrix Properties ◽  
The Matrix ◽  
Exciting Potential

Osteocytes make up 90–95% of the cellular content of bone and form a rich dendritic network with a vastly greater surface area than either osteoblasts or osteoclasts. Osteocytes are well positioned to play a role in bone homeostasis by interacting directly with the matrix; however, the ability for these cells to modify bone matrix remains incompletely understood. With techniques for examining the nano- and microstructure of bone matrix components including hydroxyapatite and type I collagen becoming more widespread, there is great potential to uncover novel roles for the osteocyte in maintaining bone quality. In this review, we begin with an overview of osteocyte biology and the lacunar–canalicular system. Next, we describe recent findings from in vitro models of osteocytes, focusing on the transitions in cellular phenotype as they mature. Finally, we describe historical and current research on matrix alteration by osteocytes in vivo, focusing on the exciting potential for osteocytes to directly form, degrade, and modify the mineral and collagen in their surrounding matrix.

scholarly journals Support of bone mineral deposition by regulation of pH

2018 ◽  
Vol 315 (4) ◽  
pp. C587-C597 ◽  
Author(s):  
Harry C. Blair ◽  
Quitterie C. Larrouture ◽  
Irina L. Tourkova ◽  
Li Liu ◽  
Jing Hao Bian ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Extracellular Space ◽  
Type I Collagen ◽  
Bone Matrix ◽  
Membrane Vesicles ◽  
Bone Collagen ◽  
Type I ◽  
Mineral Deposition ◽  
The Matrix ◽  
Ph Dependent

Osteoblasts secrete collagen and isolate bone matrix from extracellular space. In the matrix, alkaline phosphatase generates phosphate that combines with calcium to form mineral, liberating 8 H+ per 10 Ca+2 deposited. However, pH-dependent hydroxyapatite deposition on bone collagen had not been shown. We studied the dependency of hydroxyapatite deposition on type I collagen on pH and phosphate by surface plasmon resonance in 0–5 mM phosphate at pH 6.8–7.4. Mineral deposition saturated at <1 mM Ca2+ but was sensitive to phosphate. Mineral deposition was reversible, consistent with amorphous precipitation; stable deposition requiring EDTA removal appeared with time. At pH 6.8, little hydroxyapatite deposited on collagen; mineral accumulation increased 10-fold at pH 7.4. Previously, we showed high expression Na+/H+ exchanger (NHE) and ClC transporters in osteoblasts. We hypothesized that, in combination, these move protons across osteoblasts to the general extracellular space. We made osteoblast membrane vesicles by nitrogen cavitation and used acridine orange quenching to characterize proton transport. We found H+ transport dependent on gradients of chloride or sodium, consistent with apical osteoblast ClC family Cl−,H+ antiporters and basolateral osteoblast NHE family Na+/H+ exchangers. Little, if any, active H+ transport, supported by ATP, occurred. Major transporters include cariporide-sensitive NHE1 in basolateral membranes and ClC3 and ClC5 in apical osteoblast membranes. The mineralization inhibitor levamisole reduced bone formation and expression of alkaline phosphatase, NHE1, and ClC5. We conclude that mineral deposition in bone collagen is pH-dependent, in keeping with H+ removal by Cl−,H+ antiporters and Na+/H+-exchangers. Periodic orientation hydroxyapatite is organized on type I collagen-coiled coils.

scholarly journals Direct Perfusion Improves Redifferentiation of Human Chondrocytes in Fibrin Hydrogel with the Deposition of Cartilage Pericellular Matrix

2021 ◽  
Vol 11 (19) ◽  
pp. 8923
Author(s):  
Alexandre Dufour ◽  
Frédéric Mallein-Gerin ◽  
Emeline Perrier-Groult
Keyword(s):  
Type I Collagen ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Type I ◽  
Pericellular Matrix ◽  
Fibrin Gels ◽  
Matrix Quality ◽  
The Matrix ◽  
Cartilage Injuries ◽  
Main Component

Articular cartilage has limited potential for self-repair, and cell-based strategies combining scaffolds and chondrocytes are currently used to treat cartilage injuries. However, achieving a satisfying level of cell redifferentiation following expansion remains challenging. Hydrogels and perfusion bioreactors are known to exert beneficial cues on chondrocytes; however, the effect of a combined approach on the quality of cartilage matrix deposited by cells is not fully understood. Here, we combined soluble factors (BMP-2, Insulin, and Triiodothyronine, that is, BIT), fibrin hydrogel, direct perfusion and human articular chondrocytes (HACs) to engineer large cartilage tissues. Following cell expansion, cells were embedded in fibrin gels and cultivated under either static or perfusion conditions. The nature of the matrix synthesized was assessed by Western blotting and immunohistochemistry. The stability of cartilage grafts and integration with native tissue were also investigated by subcutaneous implantation of human osteochondral cylinders in nude mice. Perfusion preconditioning improved matrix quality and spatial distribution. Specifically, perfusion preconditioning resulted in a matrix rich in type II collagen but not in type I collagen, indicating the reconstruction of hyaline cartilage. Remarkably, the production of type VI collagen, the main component of the pericellular matrix, was also increased, indicating that chondrocytes were connecting to the hyaline matrix they produced.

Collagen-the Ultrastructural Element of the Bone Matrix

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.

scholarly journals Transcriptomics Study to Determine the Molecular Mechanism by which sIL-13Rα2-Fc Inhibits Caudal Intervertebral Disc Degeneration in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xin Wang ◽  
Jianshi Tan ◽  
Junhao Sun ◽  
Pengzhong Fang ◽  
Jinlei Chen ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Type I ◽  
Model Group ◽  
Expression Levels ◽  
Protein Levels ◽  
Collagen Protein

Background. Intervertebral disc degeneration is related to tissue fibrosis. ADAMTS can degrade the important components of the ECM during the process of intervertebral disc degeneration, ultimately resulting in the loss of intervertebral disc function. sIL-13Rα2-Fc can inhibit fibrosis and slow down the degeneration process, but the mechanism involved remains unclear. Objective. To determine the mechanism by which sIL-13Rα2-Fc inhibits ECM degradation and reduces intervertebral disc tissue fibrosis using a transcriptomics analysis. Methods. A rat model of caudal intervertebral disc degeneration was established, and Sirius red staining was used to observe the pathological changes in the caudal intervertebral disc. Transcriptome sequencing was employed to assess the gene expression profiles of the intervertebral disc tissues in the model group and the sIL-13Rα2-Fc-treated group. Differentially expressed genes were identified and analyzed using GO annotation and KEGG pathway analyses. Real-time fluorescence quantitative PCR was used to verify the expression levels of candidate genes. The levels of GAG and HA were quantitatively assessed by ELISA, and the levels of collagen I and collagen II were analyzed by western blotting. Results. Sirius red staining showed that in the model group, the annulus fibrosus was disordered, the number of breaks increased, and the type I collagen protein levels increased, whereas in the sIL-13Rα2-Fc group, the annulus fibrosus was ordered, the number of breaks decreased, and the type II collagen protein levels increased. In comparison with the model group, we identified 58 differentially expressed genes in the sIL-13Rα2-Fc group, and these were involved in 35 signaling pathways. Compared with those in the model group, the mRNA expression levels of Rnux1, Sod2, and Tnfaip6 in the IL-13Rα2-Fc group were upregulated, and the mRNA expression levels of Aldh3a1, Galnt3, Fgf1, Celsr1, and Adamts8 were downregulated; these results were verified by real-time fluorescence quantitative PCR. TIMP-1 (an ADAMTS inhibitor) and TIMP-1 combined with the sIL-13Rα2-Fc intervention increased the levels of GAG and HA, inhibited the expression of type I collagen, and promoted the expression of type II collagen. Conclusion. Adamts8 may participate in the degradation of ECM components such as GAG and HA and lead to an imbalance in the ECM of the intervertebral disc, resulting in intervertebral disc degeneration. sIL-13Rα2-Fc promoted anabolism of the ECM and increased the levels of ECM components by inhibiting the expression of Adamts8, thus maintaining the dynamic equilibrium of the ECM and ultimately delaying intervertebral disc degeneration.

scholarly journals Effect of protein restriction on the messenger RNA contents of bone-matrix proteins, insulin-like growth factors and insulin-like growth factor binding proteins in femur of ovariectomized rats

1996 ◽  
Vol 75 (6) ◽  
pp. 811-823 ◽  
Author(s):  
Yusuke Higashi ◽  
Asako Takenaka ◽  
Shin-Ichiro Takahashi ◽  
Tadashi Noguchi
Keyword(s):  
Dietary Protein ◽  
Type I Collagen ◽  
Control Diet ◽  
Bone Matrix ◽  
Protein Restriction ◽  
Matrix Proteins ◽  
Type I ◽  
Bone Matrix Proteins ◽  
Mrna Content ◽  
Insulin Like Growth Factors

It has been reported that loss of ovarian oestrogen after menopause or by ovariectomy causes osteoporosis. In order to elucidate the effect of dietary protein restriction on bone metabolism after ovariectomy, we fed ovariectomized young female rats on a casein-based diet (50g/kg diet (protein restriction) or 200g/kg diet (control)) for 3 weeks and measured mRNA contents of bone-matrix proteins such as osteocalcin, osteopontin and α1 type I collagen, insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) in femur. Ovariectomy decreased the weight of fat-free dry bone and increased urinary excretion of pyridinium cross-links significantly, although dietary protein restriction did not affect them. Neither ovariectomy nor protein restriction affected the content of mRNA of osteopontin and osteocalcin; however, ovariectomy increased and protein restriction extensively decreased the α1 type I collagen mRNA content in bone tissues. Ovariectomy increased IGF-I mRNA only in the rats fed on the control diet. Conversely, protein rest riction increased and ovariectomy decreased the IGF-II mRNA content in femur. Furthermore, the contents of IGFBP-2, IGFBP-4 and IGFBP-5 mRNA increased, but the content of IGFBP-3 mRNA decreased in femur of the rats fed on the protein-restricted diet. In particular, ovariectomy decreased the IGFBP-2 mRNA content in the protein-restricted rats and the IGFBP-6 mRNA content in the rats fed on the control diet. These results clearly show that the mRNA for some of the proteins which have been shown to be involved in bone formation are regulated by both quantity of dietary proteins and ovarian hormones.

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.

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