Bone matrix formation

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... 

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. 

Therapy. Formation of new bone matrix is induced by fluoride. Administered as sodium fluoride, it stimulates osteoblasts. Fluoride is substituted for Liillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

The insoluble Ca(II) salts of weak acids, such as calcium phosphate, carbonate, and oxalate, serve as the hard structural material in bone, dentine, enamel, shells, etc. About 99% of the calcium found in the human body appears in mineral form in the bones and teeth. Calcium accounts for approximately 2% of body weight (18,19). The mineral in bones and teeth is mosdy hydroxyapatite [1306-06-5] having unit cell composition Ca10(PO4)6(OH)2. The mineralization process in bone follows prior protein matrix formation. A calcium pumping mechanism raises the concentrations of Ca(II) and phosphate within bone cells to the level of supersaturation. Granules of amorphous calcium phosphate precipitate and are released to the outside of the bone cell. There the amorphous calcium phosphate, which may make up as much as 30—40% of the mineral in adult bone, is recrystallized to crystallites of hydroxyapatite preferentially at bone collagen sites. These small crystallites do not exceed 10 nm in diameter (20). 

Certain human populations depend on dietary sources of vitamin D because of insufficient biosynthesis of the vitamin due to inadequate skin exposure to sunlight. The classic symptoms of vitamin D deficiency are rickets in children and osteomalacia in adults. 25-Hydroxyvitamin D3 is the major circulating metabolite in the blood, but the hormonally active form of the vitamin is 1,25-dihydroxyvitamin D3. The latter metabolite stimulates the intestine to absorb calcium and phosphate by two independent mechanisms and acts with parathyroid hormone to mobilize calcium, accompanied by phosphate, from the bone fluid compartment into the bloodstream. 1,25-dihydroxyvitamin D 3 is also involved in the formation of osteoclasts—giant cells that are solely responsible for the resorption of bone matrix (33). Resorption is an essential process for the development, growth, maintenance, and repair of bone. 

Radium, similarly to calcium, deposits in bone within those areas where new bone mineral is being formed and also on all bone surfaces. Radium remains in those areas of new bone formation, but the radium deposits on bone surfaces eventually move into the depths of compact bone as new bone matrix is deposited on top of them. In this deposition process, short-lived radium-224 rapidly decays, leaving no radioactivity within bone whereas, long-lived radium-226 remains in the skeleton indefinitely (Rowland 1966). Mays et al. (1975) have demonstrated that the radon to radium ratio in bone increased with time after injection in beagles. 

The inorganic component of bone is primarily platelike (20 to 80 nm long and 2 to 5 nm thick) crystalhne hydroxyapatite, Ca5(P04)3(0H) or HA (Kaplan et al., 1994 Park and Lakes, 1992). Small amounts of impurities may be present in the mineralized HA matrix for example, carbonate may replace phosphate groups, whereas chloride and fluoride may replace hydroxyl groups. Because release of ions from the mineral bone matrix controls cell-mediated functions, the presence of impurities may impact important biological aspects (and, subsequently, affect chemical and mechanical properties of bone) that are critical to normal bone function for example, impurities present in the mineralized matrix may affect cellular function(s) that influence new bone formation (Kaplan et al., 1994 Park and Lakes, 1992). 

Silicon This element is essential for growth and skeletal development in certain animal species. Silicon is currently not considered to be essential for humans, but it may be involved in the formation of connective tissue, bone matrix, atherosclerosis, hypertension, and in the aging process [14, 15]. 

It should also be mentioned that intermittent slight elevation in the plasma concentration of parathormone leads to increased formation of bone substance. The likely explanation is that, under this condition, stimulation of osteoblasts is suf cient to induce synthesis of bone matrix but not strong enough to activate osteoclasts. This strategy is applied therapeutically by administration of a fragment (amino acids 1-34) of recombinant human parathormone (teripara-tide, s.c.). 

One of the most sensitive bioassays for osteoblast and osteoclast activities in vivo is the use of ectopic models of bone formation and bone matrix resorption (38,39). Devitalized, demineralized bone powders (DBP) are subcutaneously implanted in young rats. There is a phenotypic conversion of connective cell tissue mesenchyme into cartilage. Subsequently this cartilage becomes calcified, vascularized and bone is deposited in two weeks. If mineral-containing bone particles (BP) are implanted, a different phenomenon is observed. Large multinucleated osteoclast-like cells are recruited to the site of implantation. There is a complete resorption of the BP four weeks after implantation. In collaboration with Dr. Julie Glowacki of the Harvard University School of Medicine, we took advantage of these procedures and used implants of normal DBP and BP into rats that had been maintained on the three experimental diets C, L, and D (40). 

Vaughn D. J. (1984) The influence of bone cells on the formation, and mineralization, of bone matrix. Phil. Trans. Roy. Soc. London B 304, 453-454. 

The pathogenesis of hepatic osteopathy is primarily characterized by disturbed bone formation due to (7.) reduced osteoblast surface (with the number of osteoblasts being in the normal range) and (2.) reduction in osteocalcin. The latter substance is a bone-matrix protein formed by the osteoblasts. Therefore, the serum value is considered to be a marker of osteogenesis. There is no increase in osteoclasis. The causes and risk factors of disturbed bone metabolism are manifold and not totally understood as yet. (73)... 

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