bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of nonenzymatic glycosylation of type I collagen in diabetic osteopenia
Authors: Dr. Katayama Yasuyuki , Akatsu Takuhiko , Yamamoto Michiko , Kugai Nobuo , Nagata Naokazu 
Published: February 2010

Abstract
Formation of advanced glycation end products (AGEs) in extracellular matrix (ECM) is implicated in the development of chronic diabetic complications. However, the involvement of AGEs in diabetic bone disease has not been well established. We have examined whether AGEs are increased in the bone collagen of streptozotocin-induced diabetic rats in vivo and whether glycation of type I collagen affects the functions of osteoblastic cells in vitro. During 12 weeks of observation, AGEs in collagen extracted from the tibiae of diabetic rats increased in a time-dependent manner and were significantly higher than controls at every time point. In vitro, the incubation of collagen with glucose-6-phosphate resulted in a time-dependent increase of AGEs. When osteoblastic cells isolated from fetal rat calvaria were cultured on AGE-modified type I collagen, it dose-dependently inhibited phenotypic expressions of osteoblasts. Among osteoblastic parameters, nodule formation was the most sensitive, being inhibited by ∼70% by the glycation of collagen for only 1 week. Alkaline phosphatase activity and osteocalcin secretion were inhibited by 20–30% and 15–70%, respectively, by the glycation of collagen for 1–5 weeks. These results indicate that AGE-modified collagen affects osteoblastic cell differentiation and function in vitro and suggest that similar changes occurring in vivo may contribute to diabetic osteopenia. (J Bone Miner Res 1996; 11:931–937)
Limited chondro-osteogenesis by recombinant human transforming growth factor-β1 in calvarial defects of adult baboons (papio ursinus)
Authors: Ripamonti U. , Bosch C. , Van Den Heever B. , Duneas N. , Melsen B. , Ebner R. 
Published: February 2010

Abstract
The therapeutic utility of a single application of recombinant human transforming growth factor-β (hTGF-β) has not been previously tested in large osseous wounds in primates. Sixteen calvarial defects, 25 mm in diameter, were prepared in four adult male baboons (Papio ursinus). In each animal, three defects were treated with increasing doses of hTGF-β1 in conjunction with baboon insoluble collagenous bone matrix as carrier (5, 30, and 100 μg of hTGF-β1/g of matrix). The fourth defect was implanted with collagenous matrix without hTGF-β1 as control. Serial undecalcified sections were prepared from the specimens harvested on day 30. Islands of cartilage and endochondral osteogenesis were found in hTGF-β1-treated defects, irrespective of the doses used. Histomorphometry of the defect site showed no significant differences between control and hTGF-β1-treated specimens with regard to bone and osteoid volumes. However, analysis of the regenerated tissue in proximity to the defect margins only showed that, on average, greater amounts of bone formed in specimens that were treated with 5 and 30 μg of hTGF-β1 when compared with controls. This suggests a possible effect on osteoblastic cells originating from the periosteal and endosteal spaces of the severed calvaria. Overall, however, this difference has no therapeutic implications for the healing of large cranial wounds in primates. The present findings indicate that a single application of hTGF-β1, in conjunction with collagenous matrix, results in limited chondro-osteogenesis in defects of membranous bone of adult baboons. (J Bone Miner Res 1996;11:938-945)
Assessment of cancellous bone structure: Comparison of strut analysis, trabecular bone pattern factor, and marrow space star volume
Authors: Croucher Peter I. , Garrahan Nigel J. , Compston Juliet E. 
Published: February 2010

Abstract
Cancellous bone architecture is an important determinant of bone strength. Recently, several approaches to the assessment of bone structure in histological sections have been described; however, no comparative studies of these different methods have been reported. We have developed computerized methods for the simultaneous assessment of several indices of bone structure, including trabecular bone pattern factor, marrow space star volume, node-to-terminus ratio, trabecular number, and trabecular separation. The relationships between these variables has been examined in iliac crest cancellous bone obtained from 41 healthy subjects, 17 male and 24 female, aged 20–80 years (mean 47.9 years). All structural indices assessed showed significant correlations with cancellous bone area (p &lt; 0.0001). Values for trabecular bone pattern factor and marrow space volume were highly correlated (r = 0.789; p &lt; 0.0001). A comparison of indices obtained by strut analysis with trabecular bone pattern factor and marrow space star volume also revealed significant relationships, especially for the terminus-to-terminus strut length (r = 0.704 and r = 0.634, respectively; p &lt; 0.0001) and node to terminus ratio (r = −0.947 and r = −0.788, respectively; p &lt; 0.0001). The node-to-terminus ratio and trabecular bone pattern factor showed significant relationships with age which were independent of sex, cancellous bone area and trabecular width (p &lt; 0.01 and p &lt; 0.005, respectively). Our results demonstrate strong correlations between the different two-dimensional indices of bone structure in cancellous bone from healthy subjects. Trabecular penetration is likely to be an important determinant of all these variables, which may therefore reflect connectivity; however, direct comparison of these methods with three-dimensional techniques is required to establish their true relationship to bone structure. (J Bone Miner Res 1996;11:955-961)
The impact of total enteral nutrition on distraction osteogenesis in a rat model
Authors: Dr. Lumpkin C. K. , Aronson J. , Shen X. C. , Gao G. G. , Skinner R. A. , Badger T. M. 
Published: February 2010

AbstractLimb lengthening by gradual mechanical distraction, termed distraction osteogenesis (DO), results in new bone formation. We have developed a rat tibial model for DO and have proceeded to study the effects of nutrition on this process. We have combined the intragastric diet delivery system of total enteral nutrition (TEN) with DO in the rat model. The first study was designed to address the weight loss associated with DO in dogs and patients. Rats in the chow + DO group lost 10% body weight over the 20-day distraction period but gradually gained weight back to the preoperative level by the end of the 5th week of the bone consolidation period. In contrast, in the TEN + DO group, a weight gain was recorded during the 20-day distraction phase. A second study was conducted to determine the effects of TEN on the rate and histology of regenerate bone formation. The weight changes replicated those seen in the first study. Standardized radiographs, taken on day 20, revealed increases (p &gt; 0.003) in regenerate bone formation in the TEN group when compared with the chow group. Increased numbers of osteoclasts in the TEN group may indicate an accelerated entry into the remodeling phase of consolidation. Serum IGF-I values, taken at day 20, did not differ between the groups. These results demonstrate that the nutritional support dramatically increased the mineralized bone formed over the 20-day distraction period. (J Bone Miner Res 1996;11:962–969)
Effects of hysterectomy on bone in intact rats, ovariectomized rats, and ovariectomized rats treated with estrogen
Authors: Dr. Goulding Ailsa , Gold E. , Lewis-Barned N. J. 
Published: February 2010

Abstract
To determine whether the uterus plays any role in mediating the ability of estrogen to conserve bone in the rat, eight groups of animals (n = 8) with their skeletons labeled with 45Ca were studied. Rats were ovariectomized (OVX), hysterectomized (Hyst), or given sham operations (Sham) and then pair-fed a low-hydroxyproline casein diet for 4 weeks. The groups were treated orally with 17β-estradiol (E2) or vehicle, and serial measurements of biochemical markers of bone breakdown were made in weeks 1, 2, and 4. The femur density was measured by dual-energy X-ray absorptiometry (DXA), and skeletal calcium and 45Ca content were determined chemically. Final total body calcium values (mg) in the eight treatment groups were (means ± SD): Sham, 2573 ± 179; Sham + E2, 2635 ± 159; Hyst, 2537 ± 151; Hyst + E2, 2410 ± 151; OVX, 2189 ± 146; OVX + E2, 2559 ± 172; OVX/Hyst, 2138 ± 132; and OVX/Hyst + E2, 2460 ± 140. Ovariectomy raised biochemical markers of bone resorption (urinary 45Ca, hydroxyproline, and deoxypyridinoline), lowered DXA bone mineral density, and reduced total body calcium and 45Ca content in both Hyst and Sham-Hyst animals (p &lt; 0.001), whereas E2 treatment prevented these changes. Hysterectomy did not impair the ability of E2 to conserve bone in OVX rats. Thus, we conclude that estrogen-mediated induction of growth factors from uterine tissue does not play an essential role in mediating the bone-conserving actions of estrogen in the rat. (J Bone Miner Res 1996;11:977-983)
Influence of Ca2+ concentration on the clearance and circulating levels of intact and carboxy-terminal iPTH in pentobarbital-anesthetized dogs
Authors: D'Amour P. , Rousseau L. , Rocheleau B. , Pomier-Layrargues G. , Huet P.M. 
Published: February 2010

Abstract
The role of hormone secretion and hormone clearance in the differential control of circulating levels of intact (I-) and carboxy-terminal (C-) immunoreactive parathyroid hormone (iPTH) was evaluated in 18 pentobarbital-anesthetized dogs. Catheters were installed in the aorta, left renal, and hepatic veins for sampling. Hepatic and renal blood flows were calculated from sulfobromophtalein (BSP) and p-aminohippuric acid (PAH) extraction and clearance. I- and C-iPTH were measured during a 1 h of infusion of CaCl2 or Na2EDTA. High-performance liquid chromatography (HPLC) profiles of I- and C-iPTH in and out of the liver and kidney were also obtained. Data on two dogs (one CaCl2 and one Na2EDTA infusion) were pooled for the analysis of one parathyroid function using a four-parameter mathematical model. Results obtained in the basal state and during analysis of the parathyroid function were also compared with those of 24 awakened dogs. Results are means ± SD. Anesthetized dogs had lower levels of Ca2+ (1.29 ± 0.03 vs. 1.34 ± 0.04 mmol/l; p &lt; 0.001) and higher levels of I- (11.5 ± 5.7 vs. 3.0 ± 1.9 pmol/l, p &lt; 0.001) and C-iPTH (52 ± 20.9 vs. 22.8 ± 10.5 pmol/l; p &lt; 0.001) than awakened dogs. Their stimulated (S) and nonsuppressible (NS) I-iPTH levels were increased 2- and 4-fold, respectively, while similar C-iPTH levels rose only 1.35- and 1.75-fold; this caused their S (4.4 ± 0.7 vs. 6.8 ± 1.9; p &lt; 0.001) and NS (24.6 ± 11.8 vs. 49.8 ± 27.5; p &lt; 0.05) C-iPTH/I-iPTH ratios to decrease. This was not explained by different renal clearance rates of I- and C-iPTH since both were similar at ∼10 ml/kg/minute and unaffected by Ca2+ concentration. Clearance of all I- and C-iPTH HPLC molecular forms by the kidney appeared equal. A 50% decrease in the hepatic clearance of I-iPTH to ∼12 ml/kg/minute in pentobarbital-anesthetized dogs, related to a lower hepatic blood flow, explained the higher levels of S and NS I-iPTH in these animals. I-iPTH hepatic clearance was unaffected by Ca2+ concentration. C-iPTH hepatic clearance was much lower at ∼5 ml/kg/minute, abolished by hypercalcemia, and reduced by the influence of anesthesia on hepatic blood flow. This also explained the higher S C-iPTH levels in anesthetized animals. I-PTH(1–84) detected by the C-iPTH assay explained only 37.6% of the hepatic C-iPTH clearance in hypocalcemia and 73.3% in hypercalcemia. Overall, our results indicate that total C-iPTH clearance is about 40.2% that of I-iPTH in hypocalcemia and 41.3% in hypercalcemia. This would only explain a 2.4- to 2.5-fold difference in circulating levels of I- and C-iPTH if secretion rates were equal; the larger difference observed in S and NS C-iPTH/ I-iPTH ratio values is thus mainly explained by different production rates.
Effect of parathyroid hormone on renal calbindin-D28k
Authors: Hemmingsen Claus , Staun Michael , Lewin Ewa , Nielsen Palle K. , Olgaard Klaus 
Published: February 2010

Abstract
The present investigation was conducted to examine the effects of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) on renal calbindin-D28k in rats. Four groups of studies were performed: (1) parathyroidectomy (PTX) or a sham operation followed by infusion of 1,25-dihydroxyvitamin D (1,25[OH]2D) or vehicle; (2) infusions of PTH(1-34), PTH(1-84), 1,25(OH)2D, or vehicle; (3) infusion of PTHrP(1-34), PTHrP (1-86), PTH(1-34), or vehicle; and (4) injections of calcium or vehicle. PTX reduced renal calbindin-D28k levels even when plasma concentrations of 1,25(OH)2D were kept constant by infusion of 1,25(OH)2D. Infusions of PTH(1-34), PTH(1-84), and 1,25(OH)2D all increased renal calbindin-D28k and plasma calcium, whereas PTHrP(1-34) and PTHrP(1-86) increased renal calbindin-D28k before an increase of plasma calcium took place. Hypercalcemia induced by the injection of calcium did not affect the levels of renal calbindin-D28k. The present data suggest that PTH and PTHrP exert a direct effect on renal calbindin-D28k, which is not mediated by changes of 1,25(OH)2D or calcium.
The influence of growth hormone on cancellous and cortical bone of the vertebral body in aged rats
Authors: Andreassen Troels T. , Melsen Flemming , Oxlund Hans 
Published: February 2010

Abstract
The influence of growth hormone administration on cancellous and cortical bone of the vertebral body in 2-year-old male rats has been investigated. All rats were injected for 80 days, then killed. Controls were given saline, and three recombinant human growth hormone (rhGH) injected groups were given either rhGH (2.7 mg/kg/day) for the first 20 or 40 days, followed by saline injection, or rhGH for all 80 days. Tetracycline labeling was performed on days 41 and 69. In all groups given rhGH, an increase in the cortical bone volume was found. In the rhGH 40-day group, single labeling corresponding to injection on day 41 was seen all around the anterior surface of the vertebral body wall (toward the abdominal cavity). In the rhGH 80-day group, double labeling was seen all around the anterior surface of the vertebral body, and a substantial increase in the mineralizing surface/total surface, mineral apposition rate, and mineralized bone formation rate was found. In the cortical bone of the anterior wall, cavities had developed in the rhGH 40- and 80-day groups. In the cancellous bone, no differences in bone volume, bone volume/total volume, or bone surface/bone volume were seen, but in the middle part of the vertebral body a decrease in the mineralizing surface/total surface was found in the rhGH 80-day group. The height of the vertebral body was not influenced by rhGH administration, whereas the transversal and midsaggital diameters were increased in the rhGH 80-day group. The compressive mechanical strength of the vertebral body specimens was increased in the rhGH 80-day group, and this increase most likely could be explained by formation and deposition of cortical bone.
Evidence that interleukin-1, but not interleukin-6, affects costochondral chondrocyte proliferation, differentiation, and matrix synthesis through an autocrine pathway
Authors: Horan J. , Dean D.D. , Kieswetter K. , Schwartz Z. , Boyan B.D. 
Published: February 2010

Abstract
Although the effects of interleukin-1 (IL-1) and interleukin-6 (IL-6) on articular cartilage chondrocytes have been reported, little is known concerning the effects of these cytokines on growth plate chondrocytes. In this study, we examined the effect of IL-1α, IL-1β, and IL-6 on growth plate chondrocyte proliferation, differentiation, and matrix production as a function of cell maturation and examined the ability of these cells to produce IL-1α and IL-1β. Confluent fourth passage cultures of rat costochondral resting zone and growth zone chondrocytes were treated with 0–100 ng/ml of IL-1α, IL-1β, or IL-6 for 24 h and then assayed for [3H]-thymidine incorporation, alkaline phosphatase specific activity, [35S]-sulfate incorporation, and percent collagen production. Neutralizing polyclonal antibodies were used to confirm the specificity of response to each cytokine. Treatment of resting zone cells with IL-1α produced a significant, dose-dependent decrease in [3H]-thymidine incorporation, while similarly treated growth zone cells were unaffected by treatment with this cytokine. IL-1α also stimulated alkaline phosphatase specific activity and inhibited [35S]-sulfate incorporation by resting zone chondrocytes, but had no affect on growth zone chondrocytes. When collagen production was examined, it was observed that IL-1α had a stimulatory affect on growth zone cells but no affect on resting zone cells. When the effect of IL-1β was examined, it was observed that this cytokine inhibited [3H]-thymidine incorporation by resting zone cells and stimulated isotope incorporation in growth zone cells. IL-1β also stimulated alkaline phosphatase specific activity and inhibited [35S]-sulfate incorporation by resting zone chondrocytes but had no affect on growth zone chondrocytes. In contrast to IL-1α, IL-1β stimulated collagen production by resting zone cells but not growth zone cells. IL-6 had no affect on any of the parameters measured in either cell type. When cytokine production was measured, it was found that IL-1α was produced by both cell types, while IL-1β was produced only by resting zone cells. Resting zone cells secreted both IL-1α and IL-1β into the media, but 75% of the total cytokine produced by these cells was retained in the cell layer. In contrast, growth zone cells did not secrete measurable IL-1α into the media. These results suggest that IL-1α and IL-1β target resting zone cells, inducing them to differentiate and acquire a phenotype characteristic of the more mature growth zone cells. Moreover, resting zone chondrocytes produce both IL-1α and IL-1β, suggesting the possibility of an autocrine effect of these cytokines on the cells.
Surface adhesion-mediated regulation of chondrocyte-specific gene expression in the nontransformed RCJ 3.1c5.18 rat chondrocyte cell line
Authors: Mcdougall Skye , Fu Y-Hsien , Lowe Gina N. , Williams Alexia , Polendo Ruben , Benya Paul D. , Iida-Klein Akiko , Fang Meika A. , Hahn Theodore J. 
Published: February 2010

Abstract
Recent evidence suggests that decreased chondrocyte function in osteoarthritis and other articular disorders may be due to chondrocyte dedifferentiation produced by altered regulatory signals from the cartilage extracellular matrix (ECM). However, there are currently no mammalian chondrocytic cell line systems adapted to the study of this process. We therefore examined the effects of ECM growth conditions on markers of differentiated chondrocytic phenotype expression in the nontransformed rat RCJ 3.1C5.18 (RCJ) chondrocyte cell line, including type II collagen expression, aggrecan production, link protein gene expression, and parathyroid hormone (PTH) receptor number. RCJ cells grown in monolayer on plastic exhibited a dedifferentiated phenotype characterized by flattened cell morphology, with &gt;80% type I collagen and &lt;5% type II collagen production, as determined by two-dimensional gel mapping electrophoresis of collagen cyanogen bromide peptides. In addition, aggrecan production was low, and link protein mRNA was not expressed at detectable levels. After transfer to growth under minimal attachment conditions on the surface of a composite type I collagen/agarose (0.15%–0.8%) gel (CAG) for 7 days, RCJ cells developed a rounded, chondrocytic morphology and a pattern of differentiated, chondrocytic gene expression, with 79% type II and 8% type I collagen production. Steady-state type I and type II procollagen mRNA levels were altered in parallel with collagen protein expression. In cells grown on CAG, aggrecan production increased 6-fold, and there was a marked increase in both aggrecan core protein and link protein mRNA levels. In addition, maximal PTH-stimulated cAMP generation increased 15-fold in association with an increased PTH receptor number. Therefore, the RCJ chondrocyte cell line is highly sensitive to ECM regulation of chondrocyte-specific gene expression.
Raloxifene analog (LY117018 HCL) ameliorates cyclosporin A—Induced osteopenia in oophorectomized rats
Authors: Bowman A.R. , Sass D.A. , Marshall I. , Ma Y.F. , Liang H. , Jee W.S.S. , Epstein S. 
Published: February 2010

AbstractCyclosporin A (CsA) administered to the oophorectomized (Ox) rat exacerbates the high turnover osteopenia associated with estrogen deficiency. 17β-estradiol replacement therapy prevents this bone loss. The aim of this study was to see whether an estrogen-like compound, Raloxifene analog (LY117018 HCL, Ral) could likewise ameliorate CsA-induced osteopenia in the Ox rat. Sixty 6-month-old Sprague-Dawley rats, divided into five groups, underwent oophorectomy. One group acted as a basal group and the others received either vehicle (group B), CsA 15 mg/kg/day (group C), Ral 3 mg/kg/day (group D), or CsA 15 mg/kg/day and Ral 3 mg/kg/day (group E) for 28 days by gavage. A sixth sham operated group of 12 rats received vehicle only (group A). Rats were weighed and bled on days 0, 14, and 28 for measurement of ionized calcium, glucose, osteocalcin (BGP), 17β-estradiol, and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Tibiae were removed on day 28 for bone histomorphometry after double tetracycline and calcein labeling. Oophorectomy caused a significant gain in weight in groups B and C which was prevented by Ral in groups D and E. Randomized blood glucose levels and 1,25(OH)2D3 levels were elevated in both CsA-treated groups. Blood ionized calcium levels were lower in vehicle (group B) compared with sham (group A) on day 28. Ox (group B) had significantly higher serum BGP levels compared with sham-operated rats. Serum BGP levels were further elevated in group C compared with vehicle and were lowered in both Ral-treated groups to vehicle levels by day 28. Bone histomorphometry revealed a high turnover osteopenia with increased parameters of bone formation and resorption and loss of cancellous bone volume postoophorectomy (group B). CsA (group C) exacerbated the effects of oophorectomy. Ral (group D) completely prevented the high turnover osteopenia caused by oophorectomy and was able to attenuate substantially the effects of CsA in the Ox rat (group E). Ral therapy ameliorated CsA-induced osteopenia in the Ox rat and might prove a useful agent in preventing bone loss in postmenopausal women receiving CsA.