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Biomedical subjects

D J Baylink

Publications and source records attributed to D J Baylink.

At least 19 recordsLinked to original sources
PubMed1992

Ovariectomy selectively reduces the concentration of transforming growth factor beta in rat bone: implications for estrogen deficiency-associated bone loss.

Previous work showed that production of transforming growth factor beta (TGF-beta) by osteoblast-like rat UMR 106 cells was increased by 17 beta-estradiol at physiological concentrations. To determine whether ovariectomy alters the concentration of TGF-beta in rat long bones, female Sprague-Dawley rats were either sham-operated (n = 19) or ovariectomized (n = 19), pair-fed a semisynthetic diet for 6 weeks, and sacrificed. Tibial and femoral diaphyses were removed and extracted by demineralization. Ovariectomy lowered serum estrogen; did not alter body weight, serum magnesium, or serum 1,25-dihydroxyvitamin D; and produced only modest differences in serum calcium and phosphate concentrations. Hydroxyproline was higher and extractable protein was lower in bones from ovariectomized rats than in bones from sham-operated rats; calcium content did not differ between the two groups of animals. Ovariectomy lowered the concentration of TGF-beta in bone but did not change the concentration of insulin-like growth factors I or II compared with values in bone from control animals. The reduction of bone TGF-beta was evident 6 weeks after surgery but not at 3 weeks. Treatment of ovariectomized rats with estrogen eliminated the TGF-beta deficit. To determine whether 17 beta-estradiol increased TGF-beta production by normal bone cells, mouse osteoblasts were treated for 2 days with 17 beta-estradiol. The production of TGF-beta was increased almost 2-fold by 1 nM 17 beta-estradiol, and short-term treatment stimulated the intracellular accumulation of TGF-beta 1 mRNA. We conclude that ovariectomy reduces deposition of TGF-beta in rat bone and that diminished skeletal TGF-beta could play a role in the pathogenesis of bone loss, fractures, and microfractures that occur in estrogen-deficient states. Our results support the possibility that estrogen and bone TGF-beta may be necessary for normal maintenance of the skeleton in female rats.

Animals↗
PubMed1992

Evidence for a lack of functional receptors for nerve growth factor (NGF) in chick bone cells in vitro.

Nerve growth factor (NGF) is essential for the development and differentiation of sympathetic and sensory neurons. Recently, NGF receptors were demonstrated in non-neural cells, and several mesenchymal cell types including lymphocytes and skeletal myotubes were shown to be stimulated to proliferate by NGF. Our purpose was to examine for the presence of functional NGF receptors in osteoblasts. Bone cells from chick calvaria were used as a model; PC-12 cells derived from rat adrenal pheochromocytoma were used as positive controls. NGF was examined for functions in chick bone cells by studying effects on (1) [3H]-thymidine incorporation; (2) alkaline phosphatase (ALP) activity; and (3) protein tyrosine phosphorylation. Effects of NGF on thymidine incorporation and protein tyrosine phosphorylation by PC-12 cells were also measured. A radioreceptor assay was used to test for the presence of receptors. In chick calvarial cells, NGF had no effect on thymidine incorporation, ALP activity or protein tyrosine phosphorylation. Radioreceptor assay with bone cells showed no evidence of NGF receptors. In contrast, in PC-12 cells, NGF (1) decreased thymidine incorporation; (2) increased protein tyrosine phosphorylation; and (3) showed receptor activity by radioreceptor assay. In conclusion, unlike several other mesenchymal cell types, chick bone cells show no evidence of NGF receptors or functional responses to NGF in vitro.

Alkaline Phosphatase↗
PubMed1992

Low-amplitude, low-frequency electric field-stimulated bone cell proliferation may in part be mediated by increased IGF-II release.

We have developed an in vitro model incorporating a low-amplitude (10(-7) V/cm), low frequency (f less than 100 Hz), capacitively coupled electric field in order to study the mechanism through which an electric field may increase bone cell proliferation. Utilizing this model we have previously shown that electric field-stimulated bone cell proliferation was dependent on release of mitogen activity into the culture medium from exposed cells. The current studies were intended to characterize this mitogen activity. In these studies we found that electric field-stimulated human bone cell proliferation was associated with increased IGF-II mRNA accumulation and IGF-II secretion suggesting that IGF-II may in part mediate the increase in bone cell proliferation following electric field exposure.

Bone and Bones↗
PubMed1992

Effect of sodium fluoride on bone density in chickens.

In addition to increasing bone volume, fluoride has been demonstrated to increase ash weight and mineral density. To determine whether newly formed or older bone is most affected by fluoride treatment, bone from chickens receiving fluoridated water was fractionated into lower density (recently formed) and higher density (more mature) specific gravity fractions. Fluoride was administered to the chickens for different lengths of time (4 or 13 weeks) or at varying doses for a 4-week period (0, 4.2, 16.8 mmol/liter drinking water). Fluoride treatment caused a shift in the mineral density profile, showing an increased proportion of mineral distribution in the more mature, higher density fractions. To determine whether this density gradient shift was due to increased maturation rate of bone or decreased resorption and mineralization rates, [3H]proline and 45Ca were injected 5 days and 24 hours prior to sacrifice, respectively. The distributions of both 3H or 45Ca, as percentages of total counts incorporated, were shifted by fluoride treatment into more mature, higher density fractions. Expressing the number of counts as a percent of the bone in each fraction (total hydroxyproline or Ca) revealed an increased incorporation of both 3H and 45Ca into the higher specific gravity fractions 2.0-2.2. These results suggest that fluoride treatment increases bone maturation and the rate of secondary mineralization in the cortical bone. Such changes in the quality of more mature, well-mineralized bone, in humans as well as animals, may have a significant influence on brittleness and strength.

Animals↗
PubMed1992

Incorporation of sodium fluoride into cortical bone does not impair the mechanical properties of the appendicular skeleton in rats.

Clinical studies on the use of sodium fluoride (NaF) in osteoporotic patients have demonstrated increased spinal bone mass without a reduction in vertebral fracture incidence, and a trend towards reduced appendicular bone mass with an increase in peripheral fracture incidence. As previous reports have suggested that NaF becomes incorporated into bone's crystal structure, possibly affecting bone strength, we sought to examine the relationship among bone fluoride content, bone mass, and skeletal fragility. Twenty-one-day-old female Sprague-Dawley rats were treated with four different doses of NaF. The tibiae were subjected to histomorphometric and biochemical analyses, and the femora were tested in torsion for the properties of strength, stiffness, energy storage capacity, and angular deformation. The results showed that over 50% of the skeleton in these rats was turned over in the presence of NaF. The four different doses resulted in a linear increase in bone F concentration and suggested excellent absorption and incorporation of this drug. No changes in histomorphometric indices of bone formation or turnover were found. Despite the large fraction of bone formed during NaF treatment, and the linear increase in bone fluoride content in relation to dose, there were no changes observed in any of the mechanical properties. These results suggest that, even extensive incorporation of fluoride into bone, in the absence of an effect on bone mass or remodeling, does not significantly alter its capacity to withstand mechanical loads.

Animals↗
PubMed1992

PTH stimulates the proliferation of TE-85 human osteosarcoma cells by a mechanism not involving either increased cAMP or increased secretion of IGF-I, IGF-II or TGF beta.

Injections of parathyroid hormone (PTH) result in increased bone formation in several species. Work in our laboratory and others has shown a stimulation of bone cell proliferation and growth factor production by PTH. Our purpose was to study the effects of PTH on a human bone cell line using TE-85 human osteosarcoma cells as a model. After 24 h treatment, PTH caused an increase in cell proliferation as measured by cell counts and [3H]-thymidine incorporation. Proliferation was not inhibited by an anti-transforming growth factor beta (TGF beta) antibody which could abolish stimulation by exogenous TGF beta. PTH did not stimulate cAMP production, alkaline phosphatase activity or production of insulin-like growth factors I or II (IGF-I or IGF-II) in TE-85 cells. Although basal TE-85 proliferation was slowed by incubation with the calcium channel blocking agent verapamil, PTH still caused an increase in growth rate. We conclude that PTH directly stimulates TE-85 proliferation via a mechanism not involving increased adenylate cyclase activity or increased secretion of IGF-I, IGF-II or TGF beta and may stimulate bone formation in vivo by activating some other mitogenic signal to increase bone cell proliferation.

Adenylyl Cyclases↗
PubMed1992

Growth hormone stimulates cortical bone formation in immature hypophysectomized rats.

Daily subcutaneous injections of rat derived growth hormone to immature, hypophysectomized rats stimulated significant increases in body weight gain, serum osteocalcin, skeletal alkaline phosphatase and incorporation of radioactive thymidine and proline into the compact bone of femurs and tibiae. Equimolar doses of insulin-like growth factor-II did not produce similar biological effects. The data support the contention that growth hormone at equimolar concentration is a stronger osteogenic agent than is insulin-like growth factor-II in vivo.

Alkaline Phosphatase↗
PubMed1992

The 24/25-kDa serum insulin-like growth factor-binding protein is increased in elderly women with hip and spine fractures.

Fractures of the hip in elderly women represent a clinical syndrome (age-related osteoporosis) often marked by decreased calcium absorption and secondary hyperparathyroidism. We studied 13 elderly women with fractures of the hip and spine and 18 healthy similarly aged control women to determine whether serum insulin-like growth factor-I (IGF-I) or its carrier binding proteins (IGFBPs) were altered in this syndrome. Serum IGF-I concentrations were not different in the two groups (P = 0.50), but immunoreactive PTH was significantly higher in the fracture group (58.50 +/- 8.20 vs. 13.50 +/- 2.70 ng/L; P less than 0.003). Binding of [125I]IGF-I to IGFBP-3, IGFBP-2, and IGFBP-1, measured by ligand blotting, was not statistically different in the 2 groups, but binding intensities for the serum 24/25-kDa IGFBP were approximately 2.5 times greater in fracture women than control women (P less than 0.0005). In data pooled from both groups, PTH correlated strongly (r = 0.70; P less than 0.0001) with the relative binding intensities for the 24/25-kDa IGFBP. Based on previous work, we speculate that production of the 24/25-kDa IGFBP, which in vitro is known to inhibit IGF-I- and IGF-II-mediated osteoblast function, may be stimulated by PTH in patients with the syndrome of age-related osteoporosis.

Aged↗
PubMed1992

Hip mineral density in females with a recent hip fracture.

To evaluate the role of local bone mineral density (BMD) in the etiology of hip fractures, we measured the hip BMD using dual photon absorptiometry in 29 females who had recently suffered a hip fracture associated with minimal or moderate, but not major, trauma and compared their BMD to those of 14 young normal females, 58 early postmenopausal normal females, 13 age-matched normal females, and 114 spinal osteoporotic females without a hip fracture. Hip-fractured patients had a BMD significantly lower (P less than 0.001) than that of all other studied groups, suggesting that a low hip BMD is associated with hip fracture risk. A femoral neck BMD below 0.75 g/cm2 suggests an increased likelihood for developing a hip fracture. Peak BMD was measured at 1.03 g/cm2, a value comparable to published normative data. Thus, a loss in hip BMD of approximately 30% from peak mineral density appears necessary before a hip fracture may occur after moderate trauma.

Adult↗
PubMed1992

Prevention and treatment of glucocorticoid-induced osteoporosis. A pathogenetic perspective.

Since the discovery of cortisol and the synthesis of related compounds, these potent pharmacologic agents have been progressively more widely utilized in allergic, pulmonary, and rheumatologic conditions. Organ transplantation represents a new group of patients added to the already large pool of subjects receiving glucocorticoids. However, glucocorticoids cause major side effects involving several organ systems, including the cardiovascular, endocrine, gastrointestinal, ophthalmologic, and musculoskeletal systems. Among the most dramatic side effects is the development of glucocorticoid-induced osteoporosis. Glucocorticoid use in the treatment of chronic obstructive pulmonary disease accounts for the majority of male patients with osteoporosis seen in our mineral metabolism clinic. This article focuses on glucocorticoid-induced osteoporosis in the adult with an emphasis on the clinical aspects of this condition. It is intended not as an extensive review on the subject but as a practical guide to help clinicians prevent and treat this condition in adult patients.

Bone Remodeling↗
PubMed1992

Progesterone and promegestone stimulate human bone cell proliferation and insulin-like growth factor-2 production.

Recent clinical studies suggest that progesterone may be involved in the regulation of bone turnover and could promote bone formation. This study was undertaken to evaluate whether progesterone and promegestone (a 19 nor-PG derivative) may have a direct effect on human bone cells and, if so, whether growth factor production could be involved in promoting this effect. The osteosarcoma cell line TE85 and untransformed normal human osteoblastic cells derived from iliac crest were used as in vitro model systems. Progesterone and promegestone were found to significantly increase [3H]thymidine incorporation in TE85 cells in a dose-dependent manner at concentrations ranging from 10(-12) to 10(-8) mol/l after four days of cultivation (p less than 0.01, ANOVA). Consistent with this response in the TE85 cells, progesterone and promegestone increased cell number in human osteoblastic cells after six days of treatment (p less than 0.05, ANOVA). To determine whether this effect on cell proliferation was mediated by the insulin-like growth factor (IGF) regulatory system, the levels of IGF-1, IGF-2 and IGF binding protein (IGFBP) were measured in the conditioned media of both TE85 and human osteoblast cells. While no significant changes in IGF-1 levels were found in the conditioned media of progesterone and promegestone treated cultures, progesterone and promegestone at the concentration of 5 nmol/l significantly increased IGF-2 levels 2.4 and 1.5-fold respectively, at 48 h in the conditioned medium of TE85 cells as compared to control. Similarly, a 4.1 and 1.9-fold increase in IGF-2 levels was found upon treatment with progesterone and promegestone in human osteoblastic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone and Bones↗
PubMed1992

Studies on regulation of insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-4 production in human bone cells.

Previous studies have shown that the actions of IGF-II in bone are determined not only by its concentration, but also by the concentration of IGFBP-4 as well as other IGFBPs. In this study, we sought to determine by Western ligand blotting the effects of growth hormone, IGF-I and IGF-II on the production of IGFBP-3 and IGFBP-4 in TE89 human osteosarcoma cells and in untransformed normal human bone cells derived from rib. Human growth hormone at 10 micrograms/l decreased the amount of IGFBP-4 but had no effect on the IGFBP-3 level in the conditioned medium of low density cultures of TE89 cells and human bone cells derived from rib. Human growth hormone had no effect on IGFBP-3 or IGFBP-4 levels in the conditioned medium of high density human bone cell cultures. IGF-I and IGF-II, which increased human bone cell proliferation, decreased the level of IGFBP-4 (30% of control at 100 micrograms/l IGF-I and IGF-II) but increased the level of IGFBP-3 (3-10 fold at 100 micrograms/l IGF-I and IGF-II) after 48 h of treatment in the conditioned medium of both low and high density TE89 cell cultures. Similar changes in IGFBP-3 and IGFBP-4 levels were also seen in the conditioned medium of human bone cells derived from rib after treatment with IGF-I and IGF-II. Studies to determine the underlying molecular mechanisms by which IGF-II decreased the amount of IGFBP-4 in the conditioned medium revealed that IGF-II decreased the IGFBP-4 mRNA abundance and increased the IGFBP-3 mRNA abundance in human bone cells. Based on the above findings, we conclude that the production of both IGFBP-3 and IGFBP-4 is regulated in bone cells and that local and systemic agents may modulate the responsiveness of bone cells to IGFs by regulated secretion of IGFBP-3 and IGFBP-4.

Base Sequence↗
PubMed1992

Bone-resorption markers galactosyl hydroxylysine, pyridinium crosslinks, and hydroxyproline compared.

We compared the clinical performances of four bone-resorption (BR) assays (hydroxyproline, HYP; galactosyl hydroxylysine, GHYL; deoxypyridinoline, DPD; and pyridinoline, PYD) in subjects with different BR rates: normal (adult men and premenopausal women), mildly increased (postmenopausal osteoporotic women), high (Paget disease patients), and very high (children). The discrimination power (Z score) and the accuracy (estimated by receiver-operating characteristic analysis) for GHYL, DPD, and PYD were compared with those for HYP. Discrimination power and accuracy were similar for high- and very-high-BR groups for all four assays. However in the mildly increased-BR group, DPD, GHYL, and PYD showed a higher discrimination power and accuracy than did HYP. The clinical performances of HYP, DPD, GHYL, and PYD are comparable for large changes in BR. For modest changes, DPD, GHYL, and PYD are more accurate and have a higher discrimination power than does HYP.

Adult↗
PubMed1991

Isolation of a novel insulin-like growth factor (IGF) binding protein from human bone: a potential candidate for fixing IGF-II in human bone.

Insulin-like growth factor-II (IGF-II) is the most abundant growth factor stored in human bone. Upon release from this storage depot, IGF-II could act in bone repair and in the coupling of bone formation to bone resorption, a process inherent to bone which is a key regulatory process for maintenance of bone tissue. In this study, we report the isolation and characterization of a novel IGF binding protein (IGFBP) from human bone and describe how this IGFBP may be involved in the fixation of IGF-II in human bone. This new IGFBP has an apparent molecular weight of 29 kDa and has several fold higher affinity for IGF-II than IGF-I which could explain the much greater abundance of IGF-II than IGF-I in human bone. In terms of biological activity, this IGFBP was found to potentiate the proliferative actions of IGF-II on bone cells. This work raises the possibility that this IGFBP may participate in mediating some of the actions of IGF-II.

Amino Acid Sequence↗
PubMed1991

Fluoride therapy for osteoporosis: a review of dose response, duration of treatment, and skeletal sites of action.

Osteoporosis is a disease characterized by a reduction in bone density which predisposes to fracture after even minimal trauma. Fluoride, because it has consistently been shown to stimulate bone formation and increase trabecular bone density, has been widely studied for the treatment of osteoporosis. The article focuses on the dose response, duration of treatment, and skeletal sites of action of fluoride; we also include comments on the effect of fluoride on vertebral and appendicular fracture rates. The skeletal response to fluoride doses, ranging from 15 to 43 mg elemental fluoride per day, included a linear increase in spinal bone density at an average rate of 1.25 +/- 0.91 mg/cm3 per month. The rate of increase in spinal bone density was related to the dose of fluoride (r = 0.34, P less than 0.03). Spinal bone density had increased above the fracture threshold in 44% of patients treated with fluoride for 32 +/- 10 months. The time required to achieve this goal was, however, influenced by the pretreatment spinal bone density and interpatient variation in response to fluoride treatment. Patients whose spinal bone density remained below the fracture threshold had lower pretreatment bone densities and/or slower rates of increase in spinal bone density (P less than 0.001). The osteogenic effect of fluoride was not limited to the spine. After 2 years of fluoride therapy, we found bone density in the femoral condyle (measured by QCT) to have increased by 13 +/- 2.6 mg/cm3 (n = 38, P less than 0.001); bone density in the hip (measured by DPA) was increased by 0.0261 +/- 0.015 g/cm2 (n = 55, P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗
PubMed1991

Evaluation of the usefulness of serum phosphatases and osteocalcin as serum markers in a calcium depletion-repletion rat model.

The present study examined the usefulness of the serum alkaline phosphatase (ALP) activity, osteocalcin, and tartrate-resistant acid phosphatase (TrACP) activity as bone turnover markers in a calcium depletion/repletion rat model. Weanling rats were fed calcium-deficient diet for 4 weeks, followed by 2 weeks of dietary calcium repletion. Serum phosphatases and osteocalcin were determined and compared with those of corresponding age-matched, pair-weighted controls. Rats were sacrificed at the end of each phase of the study, and bone phosphatase activities in tibiae and vertebrae were measured. During calcium depletion, rats developed hypocalcemia and lost significant bone calcium, which were reversed with dietary calcium repletion. During depletion when previously published histologic studies indicated a suppressed bone formation and stimulated bone resorption, serum ALP activity and osteocalcin levels were significantly elevated and serum TrACP activity reduced; at the same time, the bone ALP and TrACP activities were increased. Because the serum level of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) which has been shown to stimulate the synthesis of skeletal ALP and of osteocalcin, was also significantly increased during depletion, the increased serum ALP and osteocalcin level could be indirect consequences of the hypocalcemia-mediated elevation in 1,25(OH)2D3 level. These effects were reversed upon calcium repletion, during which previously published histologic studies demonstrated a stimulated bone formation and a suppressed resorption in these rats. In conclusion, although there is increasing evidence for the usefulness of these serum proteins as markers of bone metabolism in humans, a great deal more work is required before we can understand the significance of these assays. Until such is accomplished, these assays should not be assumed to be validated.

Acid Phosphatase↗
PubMed1991

Evidence that tartrate-resistant acid phosphatases from osteoclastomas and hairy cell leukemia spleen are members of a multigene family.

1. Osteoclasts and hairy cell leukemia spleen both contain large amounts of a band 5-tartrate-resistant acid phosphatase (TrACP). 2. We have recently purified to homogeneity a band 5 TrACP from human osteoclastomas and two isoforms of band 5 TrACP (5a and 5b) from the spleen of a patient with hairy cell leukemia. 3. Although the N-terminal amino acid sequences and the apparent molecular weights of the osteoclastoma, hairy cell leukemia spleen TrACPs were identical, there were several differences in the physical and biochemical properties between the three isoenzymes. 4. Based on these findings, it is concluded that these isoenzymes are different enzymes, but that they could have originated from a similar ancestral gene. 5. It is proposed that the osteoclastoma and hairy cell leukemia band 5 TrACPs are members of a multigene family.

Acid Phosphatase↗