Bone matrix

RGD analogs have been shown to inhibit the attachment of osteoclasts to bone matrix and to reduce bone resotptive activity in vitro. The cell surface integrin, av 33, appears to play a role in this process. RGD analogs may rq resent a new approach to modulating osteoclast-mediated bone resorption and may be useful in the treatment of osteoporosis [9]. 

Osteoblasts are the primary cells responsible for bone formation. They are derived from mesenchymal (stromal) cells that first differentiate into pre-osteoblasts and then into mature, bone matrix producing osteoblasts. Inactivated or resting osteoblasts become lining cells and thus a reservoir for bone forming cells to be activated at the next remodelling cycle. Osteoblasts trapped and embedded in the mineralised matrix are called osteocyts, and are important for many properties of living bone. 

Fluorid ions stimulate bone formation by a direct mitogenic effect on osteoblasts mediated via protein kinase activation and other pathways. Further to these cellular effects, fluorides alter hydroxyapatite crystals in the bone matrix. In low doses, fluorides induce lamellar bone, while at higher doses abnormal woven bone with inferior quality is formed. The effect of fluorides on normal and abnormal (e.g. osteoporotic) bone therefore depends on the dose administered. 

Recently, water-soluble protein fractions, isolated from extracts of bone matrix, were incorporated into a collagen matrix and shown to induce bone (67,68) and cartilage formation both in vitro and in vivo (69,70). In the latter studies, in the absence of the collajgen delivery system, the proteins were incapable of inducing cartilage formation in vivo when implanted intramuscularly into mice. The success of this approach appears to depend on delivering the active agents at an effective dose over an extended time period. 

K Phylloquinone, menaquinones Coenzyme in formation of y-carboxyglutamate in enzymes of blood clotting and bone matrix Impaired blood clotting, hemorrhagic disease... 

Treatment of pregnant women with warfarin can lead to fetal bone abnormalities (fetal warfarin syndrome). Two proteins are present in bone that contain y-carboxygluta-mate, osteocalcin and bone matrix Gla protein. Osteocalcin also contains hydroxyproHne, so its synthesis is dependent on both vitamins K and C in addition, its synthesis is induced by vitamin D. The release into the circulation of osteocalcin provides an index of vitamin D stams. 

The major cell types involved in bone resorption and deposition are osteoclasts and osteoblasts (Figure 48-11). The former are associated with resorption and the latter with deposition of bone. Osteocytes are descended from osteoblasts they also appear to be involved in maintenance of bone matrix but will not be discussed further here. 

Figure 48-12. Schematic illustration of some aspects of the role of the osteoclast in bone resorption. Lysosomal enzymes and hydrogen ions are released into the confined microenvironment created by the attachment between bone matrix and the peripheral clear zone of the osteoclast. The acidification of this confined space facilitates the dissolution of calcium phosphate from bone and is the optimal pH for the activity of lysosomal hydrolases. Bone matrix is thus removed, and the products of bone resorption are taken up into the cytoplasm of the osteoclast, probably digested further, and transferred into capillaries. The chemical equation shown in the figure refers to the action of carbonic anhydrase II, described in the text. (Reproduced, with permission, from Jun-queira LC, Carneiro J BasicHistology. Text Atlas, 10th ed. McGraw-Hill, 2003.)...

Aluminium toxicity is the likely cause of three human disorders arising from long-term haemodialysis vitamin D-resistant osteomalacia, iron adequate microcytic anaemia, and dialysis dementia (Martin, 1994). The first of these conditions is consistent with interference with calcium deposition into bone, and the accumulation of aluminium in the bone matrix. 

Giraud-Guille, M.M., Mosser, G., Helary, C. and Eglin, D. (2005) Bone matrix-like assemblies of collagen From liquid crystals to gels and biomimetic materials. Micron, 36, 602-608. 

From the beginning of 14C studies, bone was burdened with a marginal status as a sample type. It was missing from the list of sample materials which Libby initially recommended [10]. He and other researchers discouraged its use for the reason that the carbon content and specifically the organic carbon content, was low even in relatively recent bone and because it was a very porous structure potentially subject to chemical alteration and presumably to contamination. It was concluded that bone would systematically violate the third assumption of the 14C method as listed in Table 1. (It should be noted that "burned bone" was highly recommended. However, the sample material was the carbonized hair, skin, and other tissue rather than the bone matrix itself.)... 

Once stem cells are committed to the osteoblast lineage, proliferating osteoprogenitors become preosteoblasts, cell growth declines, and there is a progressive expression of differentiation markers by osteoblasts (Stein et al. 1996). Osteoblastic differentiation is characterized by the sequential expression of alkaline phosphatase (ALP), an early marker of osteoblastic phenotype, followed by the synthesis and deposition of collagen type I, bone matrix proteins, and glycosaminoglycans and an increased expression of os-... 

The bone becomes depleted of calcium salts when the urine is acidic over a relatively long period. This was shown by Goto (17) who fed rabbits large doses of hydrochloric acid. He then showed that urinary calcium loss occurred in concert with a marked reduction in mass of the skeletal system, and also that the total non-fat dry weight of bone decreased,implying a loss of bone matrix. A dose-dependent, dietary acid induced loss of labelled calcium from rat bone has been reported by Thorn and his coworkers (18). They demonstrated that in response to graded doses of ascorbic acid, cells in tissue culture, and bones in whole animals fed such doses were depleted of the labelled calcium. 

Embedded within the protein-mineral structure are the three types of bone cell osteoblasts ( bone builders which form new bone matrix), osteoclasts (which degrade... 

Monomeric plutonium species deposited in the liver become concentrated in the liver ferritin, the principal iron repository (191). On analysis of plutonium deposition in bone a dichotomy becomes immediately apparent. Monomeric plutonium no longer follows an iron transport/deposition mechanism, for bone contains little or no iron complexed within the bone matrix. Calcium phosphate as a chromatographic media does, of course, retain iron. 

Osteoporosis is defined as a generalized decrease in bone mass (osteopenia) that affects bone matrix and mineral content equally, giving rise to fractures of vertebral bodies with bone pain, kyphosis, and shortening of the torso. Fractures of the hip and the distal radius are also commoa The underlying process is a disequilibrium between bone formation by osteoblasts and bone resorption by osteoclasts. 

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