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Biomedical subjects

A L Boskey

Publications and source records attributed to A L Boskey.

At least 109 records · Page 6Linked to original sources
PubMed1991

The role of extracellular matrix components in dentin mineralization.

The extracellular matrix of dentin consists of mineral (hydroxyapatite), collagen, and several noncollagenous matrix proteins. These noncollagenous matrix proteins may be mediators of cell-matrix interactions, matrix maturation, and mineralization. This review describes the current knowledge of the chemistry of mineral crystal formation in dentin with special emphasis on the roles of the dentin matrix proteins. The functions of some of these matrix proteins in the mineralization process have been deduced based on in vitro studies. Functions for others have been postulated based on analogy with some of the bone matrix proteins. Evidence suggests that several of these matrix proteins may have multiple effects on nucleation, crystal growth, and orientation of dentin hydroxyapatite.

Crystallization↗
PubMed1990

Concentration-dependent effects of dentin phosphophoryn in the regulation of in vitro hydroxyapatite formation and growth.

The effect of dentin phosphophoryn on hydroxyapatite formation and growth was studied in an in vitro gelatin gel diffusion system. Phosphophoryn, in low concentrations (0.010-1 microgram/ml) promoted de novo hydroxyapatite formation; at a higher concentration (100 micrograms/ml) in the same system, the dentin matrix protein inhibited hydroxyapatite growth. Similar inhibition of hydroxyapatite growth was seen in solution. The intact phosphophoryn was not essential for either inhibition of seeded growth or promotion of mineralization, since the formic acid degraded protein was comparably effective. Transmission electron microscopy of the precipitates formed at 7 days showed no significant differences in crystallite size distribution in the presence and absence of phosphophoryn. However there was a dose-dependent decrease in the number of mineral clusters formed in the presence of increasing amounts of phosphophoryn, suggesting inhibition of secondary nucleation. These data provide support for the postulated 'multifunctional' role of the dentin phosphoprotein in the mineralization process.

Animals↗
PubMed1990

The distribution of calcific deposits in intervertebral discs of the lumbosacral spine.

The incidence of intervertebral disc calcifications (IVDCs) was examined in 52 lumbosacral spines obtained sequentially at autopsy. The presence of calcific deposits was detected by fine-grain roentgenograms. The nature of these deposits was determined by wide-angle x-ray diffraction, and histologic observations were made. A high prevalence of IVDC, 18 spines of 52, some with multiple deposits, was noted. Calcium pyrophosphate dihydrate (CPPD) deposits were found in 3% of the spines and accounted for 29% of the 42 deposits analyzed. The CPPD deposits occurred at multiple disc levels (an average of four per spine), were diffuse, and involved a major portion of the disc (nucleus pulposus, annulus fibrosus, and endplate) but were not generally associated with histologic disc degeneration. Hydroxyapatite (HA) deposits occurred in 12% of the spines, most often in the nucleus pulposus and endplate. The HA deposits appeared as small punctate radiodensities. Roentgenographic evidence of degenerative changes, i.e., disc space narrowing, endplate disruption, desiccation, and osteophyte formation, were present in all but one of the spines containing HA deposits. An additional 19% of the spines had deposits that could not be characterized by x-ray diffraction but were very similar in roentgenographic appearance to HA deposits. No conclusions could be drawn on the relationship between the presence of HA or CPPD and collagen or hexosamine content.

Adult↗
PubMed1990

Bone mineral and matrix. Are they altered in osteoporosis?

Osteoporosis is a major health threat whose etiology remains elusive. Disease heterogeneity and until recently the absence of appropriate techniques prevented detailed analyses of the underlying defects in this disease. Among the questions that must be asked are: (1) Are the cells in the osteoporotic bone functioning normally? (2) Is the matrix produced by these cells normal? (3) Is the pattern of mineral deposition normal? If not, how do each of these differ from normal, what is the effect of that abnormality, and how can it be prevented or corrected? Through answering these questions the scientific community will learn the function of many of the matrix proteins and may gain insight into revolutionary new therapies. The tools of human bone cell culture, new imaging techniques, analyses in biopsy samples, and other aspects of modern biotechnology are now available to start answering these questions.

Animals↗
PubMed1989

Noncollagenous matrix proteins and their role in mineralization.

Improved technologies have led to the isolation of a large number of noncollagenous matrix proteins from the mineralized connective tissues. These proteins have been postulated to have many functions, but few of their suggested roles have been verified. Many of the noncollagenous matrix proteins are thought to regulate the deposition of hydroxyapatite mineral. In this review the current information on the role of these proteins in the mineralized and mineralizing connective tissues is presented along with a synopsis of the methods currently being used to elucidate these functions.

Animals↗
PubMed1989

Tumoral calcinosis: seasonal biochemical studies and chemical studies of eyelid lesion.

We recently described (Arch Ophthalmol 1988; 106:725-6) the presence of unique calcific lesions in the eyelids of a young woman with a history of hyperphosphatemic tumoral calcinosis. Here we document that no immediate family members showed similar lesions and that none was hyperphosphatemic. Dental roentgenography revealed characteristic abnormalities in the patient that confirmed the clinical diagnosis of tumoral calcinosis. Seasonal biochemical studies demonstrated persistently increased concentrations of phosphorus and 1,25-dihydroxyvitamin D in her serum. A calcific eyelid excrescence removed from the patient, studied by x-ray diffraction, was found to consist of crystals of hydroxyapatite. Microprobe analysis indicated the major elements in the deposit to be Ca, P, S, and Cl, just as in the periarticular deposits found in tumoral calcinosis. The Ca concentration in the patient's tear fluid, measured by atomic absorption spectrometry, was within the range found in tears of healthy volunteers. Phosphorus was undetectable (less than 30 mumol/L) in tears of the patient and the volunteers. These findings suggest that the eyelid lesions represent a new manifestation of the pathological process that produces the characteristic periarticular calcific masses of tumoral calcinosis.

Adolescent↗
PubMed1988

The mineral and mechanical properties of bone in chronic experimental diabetes.

The long-term effects of experimentally induced diabetes on bone were studied in eight male Lewis rats, intravenously (i.v.) injected with 65 mg/kg of streptozocin (STZ) and maintained for 12 months. Eight untreated age-matched rats served as controls. In the STZ-treated rats, experimentally induced diabetes was documented by the presence of hyperglycemia at 24 h and at 3 and 12 months. Significantly less weight was gained and less growth occurred in the STZ-treated rats despite careful attention to feeding and hydration. Mineral alterations were detected in the bones of the animals with experimental diabetes. Decreased hydroxyapatite crystal perfection, decreased Ca/P of the ash, and decreased ash content in the tibial metaphyses with increased ash content in the tibial diaphyses, was noted relative to controls. Bone osteocalcin content was increased in the metaphyses of the STZ-treated rats. While absolute measures of stiffness, torsional strength and energy absorption were decreased in the bones of the STZ-treated animals, when torsional strength and stiffness were normalized for differences in both growth and geometry, the normalized stiffness values for the diabetic bones were increased. The results suggest that in experimental diabetes certain aspects of bone mineralization are adversely affected and lead to reduced strength-related properties. However, a compensatory increase in stiffness occurs. The reason for this increase, although not known, may be related to changes in bone crystal structure.

Animals↗
PubMed1988

Effect of gallium on bone mineral properties.

Gallium nitrate is biologically active in blocking bone resorption in vitro as well as in vivo. Administration of gallium nitrate to growing rats results in a dose-dependent accumulation of low levels of gallium in bone that is associated with specific changes in the mineral properties of bone. To elucidate in greater detail the changes induced by gallium, the properties of whole and density-fractionated bone samples from control and gallium-treated rats were examined. These studies showed that short-term treatment with gallium nitrate caused an increase in bone calcium and phosphate content. Devitalized bone powder from the gallium-treated rats was less soluble in acetate buffer and less readily resorbed by monocytes. Density fractionation analyses demonstrated that the largest proportion (76% by weight) of powdered metaphyseal bone particles from rats had a density of less than 2.15 g/cc. Following short-term treatment (14 days) with gallium nitrate (45 mg/kg body weight), a significant increase in the relative proportion of more dense bone (greater than or equal to 2.15 g/cc) was observed (24% for the control vs. 39% for the gallium-treated rats, P less than 0.01). In the diaphyseal samples, the largest proportion (88% by weight) of the bone powder had a density of greater than or equal to 2.15 g/cc. After short-term treatment with gallium, a slight decrease in mean diaphyseal particle density was observed. Measurement of calcium accretion with 45Ca in the gallium-treated rats demonstrated increased specific activity in the metaphyseal bone samples, densities = 2.0, 2.1, 2.15, and 2.25 g/cc; the difference was significant only for the 2.25 g/cc fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The effect of short-term treatment with vitamin D metabolites on bone lipid and mineral composition in healing vitamin D-deficient rats.

Vitamin D deficiency is known to cause alterations in the lipid and mineral components of bone and cartilage. In this study, second generation, normal phosphatemic, vitamin D-deficient rats, treated with low and high doses of three different vitamin D metabolites were sacrificed 24 h after treatment and their bones analyzed in order to determine which metabolites were most effective in altering the lipid composition. In the untreated vitamin D-deficient rats, tissues undergoing endochondral ossification (epimetaphyses), periosteal and endosteal bone formation (diaphyseal bone), and intramembranous bone formation (calvaria) all contained lower amounts of complexed acidic phospholipids, as well as decreased amounts of mineral. Twenty-four hours following treatment, the complexed acidic phospholipid content was significantly increased relative to both untreated and normal (vitamin D-replete) animals, the greatest increases occurring in animals treated with 1,25-dihydroxyvitamin D. All metabolites tested altered histomorphometric and/or mineral parameters, but only 1,25-dihydroxyvitamin D, in low and high doses, significantly increased the content of the complexed acidic phospholipids in all tissues studied. High doses of other metabolites increased complexed acidic phospholipid content in some tissues, perhaps due to their conversion to 1,25-dihydroxyvitamin D. Linear relationships between serum 1,25-dihydroxyvitamin D levels and tissue complexed acidic phospholipid content are reported. It is suggested that one way in which this metabolite may directly contribute to calcification is by facilitating formation of lipids involved in this process.

Animals↗
PubMed1988

Influence of vitamin D status on the content of complexed acidic phospholipids in chick diaphyseal bone.

Calcium acidic phospholipid phosphate complexes cause hydroxyapatite formation in vitro and in vivo. Previous studies have shown that the amount of these complexed acidic phospholipids is altered in the bones of animals depleted of vitamin D and phosphate. To help differentiate the effects of vitamin D from those due to altered mineral metabolism, the amount of complexed acidic phospholipids present in diaphyseal bone was determined in five groups of chicks varying in calcium, phosphate and vitamin D status. Highest levels of complexed acidic phospholipids were found in chicks receiving vitamin D and having normal serum levels of Ca and P. Lowest levels were found in vitamin D-deficient chicks; levels were not altered in vitamin D-deficient chicks when their serum Ca was normalized. Intermediate levels were found in vitamin D-treated chicks fed a low Ca diet. Levels of the complexed acidic phospholipids were low in bones of hypophosphatemic, vitamin D-treated chicks but, when related to total lipid phosphorus content, values were similar to those of hypocalcemic chicks. These data suggest that while disturbances in calcium and phosphate metabolism which are present in rickets influence the bone content of these complexed acidic phospholipids, vitamin D may also play a direct role in their formation. Further, the ability of vitamin D to increase bone complexed acidic phospholipid content does not seem to be related to its hypercalcemic effect.

Animals↗
PubMed1988

Calcium-acidic phospholipid-phosphate complexes in human hydroxyapatite-containing pathologic deposits.

The deposition of calcium-containing crystals in tissues is due to a combination of factors: elevation in the concentrations of precipitating ions, formation of specific nucleators, and removal of macromolecules that inhibit crystal deposition. This study tested the hypothesis that calcium acidic phospholipid phosphate complexes, which promote hydroxyapatite deposition both in vitro and in vivo, are associated only with hydroxyapatite deposits, and furthermore, that the presence of these complexes is associated with all such hydroxyapatite deposits. Lipid analysis of 76 surgical specimens containing evidence of pathologic calcification (35 hydroxyapatite, 35 calcium pyrophosphate dihydrate, and 6 containing other crystalline materials) had mean complexed acidic phospholipid contents of 8.7, 1, and 0.012, (microgram/mg demineralized dry weight) respectively. Tissues that contained larger, more perfect hydroxyapatite crystals based on x-ray diffraction analyses, had a higher complexed acidic phospholipid content (7.5 +/- 4 micrograms/mg demineralized dry weight, N = 16) than tissues with poorly crystallized hydroxyapatite (3.9 +/- 2 micrograms/mg, N = 11). Histologically, tissues containing larger crystals were characterized by cell or tissue necrosis. Poorly crystalline deposits were found in tissues showing little or no evidence of cell necrosis or tissue degeneration.

Calcinosis↗
PubMed1987

Biochemical characterization of fracture callus proteoglycans.

The changes in proteoglycan molecules during the initial stages of fracture healing in rats were characterized. Following extraction of callus proteoglycan components with dissociative solvents, the components were purified in a cesium chloride density gradient. The recovered proteoglycans were characterized with respect to their molecular size distribution using gel filtration chromatography and a centrifugal transport methodology. During this early healing period, a decrease was observed in the relative proportion of the aggregate and in the hydrodynamic size and sedimentation coefficients of these molecules. While some molecular degradation could have occurred during the early stages of fracture healing, the dominant change of the proteoglycan molecules seemed to be disaggregation. No significant difference was observed in the proportion of aggregates reformed when exogenous hyaluronate and link glycoproteins were allowed to interact with the two corresponding monomer preparations. The molecular changes of the proteoglycan molecules seem to parallel those occurring during endochondral calcification of rat epiphyseal cartilage.

Animals↗
PubMed1986

In vivo hydroxyapatite formation induced by lipids.

Proteolipids and complexed acidic phospholipids that cause in vitro hydroxyapatite formation, similarly cause hydroxyapatite deposition in 10-mu pore Millipore chambers when implanted in rabbit muscle pouches. The amount of mineral deposited during a 3-week period, based on the calcium and phosphate contents of the chambers, was directly related to the dry weight of the lipid implanted in the chamber. Chambers containing total lipid extract from rabbit bone from which the complexed acidic phospholipids had been removed, acidic phospholipids from which the the proteolipids had been removed, and empty chambers did not accumulate any detectable mineral during the course of the study. Chambers implanted with synthetic hydroxyapatite served as controls for chemical analyses. The presence of hydroxyapatite in the chambers was established 3 weeks after implantation based on electron microscopic, compositional, and wide-angle X-ray diffraction analyses of the deposits. In the cell-free chambers, lipid-induced hydroxyapatite deposition, but not bone matrix formation occurred. This study demonstrates that proteolipids and complexed acidic phospholipids can cause hydroxyapatite mineral deposition in a physiologic environment. To date, these lipids are the only materials isolated from mineralizing tissues, other than reconstituted collagen, that have been shown capable of causing in vivo mineralization in the absence of cells.

Animals↗
PubMed1986

Gallium increases bone calcium and crystallite perfection of hydroxyapatite.

Gallium, a group IIIa metal, is known to interact with hydroxyapatite as well as the cellular components of bone. In recent studies we have found gallium to be a potent inhibitor of bone resorption that is clinically effective in controlling cancer-related hypercalcemia as well as the accelerated bone resorption associated with bone metastases. To begin to elucidate gallium's mechanism of action we have examined its effects on bone mineral properties. After short-term (14 days) administration to rats, gallium nitrate produced measurable changes in bone mineral properties. Using atomic absorption spectroscopy, low levels of gallium were noted to preferentially accumulate in regions of active bone formation, 0.54 +/- .07 microgram/mg bone in the metaphyses versus 0.21 +/- .03 microgram/mg bone in the diaphyses, P less than 0.001. The bones of treated animals had increased calcium content measured spectrophotometrically. Rats injected with radiolabeled calcium during gallium treatment had greater 45-calcium content compared to control animals. By wide-angle X-ray analyses, larger and/or more perfect hydroxyapatite was observed. The combined effects of gallium on bone cell function and bone mineral may explain its clinical efficacy in blocking accelerated bone resorption.

Animals↗
PubMed1986

The effects of proteoglycans from different cartilage types on in vitro hydroxyapatite proliferation.

Proteoglycans extracted from nasal and articular cartilages have previously been shown to inhibit hydroxyapatite proliferation in vitro. This study now demonstrates that proteoglycans isolated (dissociatively extracted and reaggregated in vitro) from bovine fetal growth plate and bovine occipital condyle, as well as those from bovine nasal cartilage, all retard hydroxyapatite seeded-growth in vitro. On a weight basis (1 mg/ml), the growth plate proteoglycan preparation had a significantly greater inhibitory effect. The greater inhibitory effect of the growth plate proteoglycans as compared to the other cartilage proteoglycan preparations may be related to the unique properties of the proteoglycans in the growth plate, a tissue that undergoes physiological calcification.

Animals↗