Biosynthesis of rat growth plate proteoglycans in diabetes and malnutrition

Axelsson, Inge; Lorentzon, Ronny; Pita, Julio C.

doi:10.1007/bf02405037

Cited by 26 publications

(17 citation statements)

References 26 publications

(20 reference statements)

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“…Portions from the digested extraction residues and the clarified extracts, and the fractions from gel chromatography and ultracentrifugation, were diluted with Aquasol and the radioactivity was measured by liquid scintillation spectrometry (5).…”

Section: Studies Of [35s]-labeled Proteoglycans Twenty 25-d-old Malementioning

confidence: 99%

“…Thirty male Sprague-Dawley rats were 5 wk old when the experiments started (day 0); they were killed 8 d later (d 8). Diabetes was induced in 15 rats on d 0 by a single intravenous dose of streptozotocin (Sigma Chemical Co., St Louis, MO) (19,20) as described previously (5). Ten rats served as controls.…”

Section: Studies Of [35s]-labeled Proteoglycans Twenty 25-d-old Malementioning

confidence: 99%

“…We have described profound changes of proteoglycan metabolism in the growth plate of diabetic rats, namely a complete absence of large proteoglycan aggregates and a sharp reduction of the synthesis of sulfated glycosaminoglycans, the chains of which were shorter than in normal rats (5). Insulin-treated diabetic rats and malnourished nondiabetic rats showed changes in proteoglycan metabolism that were intermediate between normal and diabetic rats.…”

mentioning

confidence: 97%

“…This process is regulated by several hormones, including growth hormone, insulin, and somatomedins (1)(2)(3)(4)(5)(6)(7). The stimulation of growth by insulin (4)(5)(6)(7) is clinically demonstrated by the retarded growth that may occur in insulinopenic diabetic children (8).…”

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Kinetics of Proteoglycans and Cells in Growth Plate of Normal, Diabetic, and Malnourished Rats

et al. 1990

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Longitudinal growth of tubular bones takes place by cell divisions and synthesis of extracellular matrix by the chondrocytes of the growth plate. This process is regulated by several hormones, including growth hormone, insulin, and somatomedins (1-7). The stimulation of growth by insulin (4-7) is clinically demonstrated by the retarded growth that may occur in insulinopenic diabetic children (8).Bone formation is preceded by provisional calcification of the cartilage matrix. Most investigators have found that the concentration of proteoglycans decreases during calcification, which may suggest that calcification is inhibited by proteoglycans (9-12). The transformation of the large, dense proteoglycan aggregates in the proliferative and upper hypertrophic zone to the relatively small, star-like proteoglycan aggregates in preparations from rabbit growth plate (13) has been suggested to allow the movement of calcium and phosphate ions and the growth of mineral clusters ( 14). Shevard and Mitchell ( 15) did not find any decrease in prot~oglycan'concentration d u i n g calcification but described that mineralization starts with star-shaped proteoglycan aggregates as templates.We have described profound changes of proteoglycan metabolism in the growth plate of diabetic rats, namely a complete absence of large proteoglycan aggregates and a sharp reduction of the synthesis of sulfated glycosaminoglycans, the chains of which were shorter than in normal rats (5). Insulin-treated diabetic rats and malnourished nondiabetic rats showed changes in proteoglycan metabolism that were intermediate between normal and diabetic rats.Our study was designed to investigate the turnover of growth plate proteoglycans in normal rats and the morphologic changes of growth plate in diabetes and malnutrition. A preliminary report has been published (1 6). MATERIALS AND METHODS Studies of [35S]-labeled proteoglycans. Twenty 25-d-old maleSprague-Dawley rats (Charles River Breeding Laboratories, Wilmington, MA) were injected with carrier-free Na2[35S]S04 (3 pCi/g body wt; 3 pCi = 1 11 kBq) into the tail vein and killed 2, 24, 48, 72, or 96 h later by intracardial injection of sodium pentobarbital. The growth plate and adjacent calcified metaphyseal tissue were dissected from the proximal end of each tibia and'pieces were used for autoradiography or extraction of proteoglycans.Autoradiography was performed as described by Campo and Dziewiatkowski (17). Extraction and characterization of proteoglycans were performed in the following way: Pieces of cartilage were immediately after dissection placed in ice-cold 4 M guanidine-HC1 in 0.25 M sodium acetate, pH 5.8 (about 1 mL/20 mg wet tissue) containing protease inhibitors (5). The suspension was dialyzed against 20 vol of the extraction solution with magnetic stining at -12°C for 24 h and then centrifuged at 8°C in a Beckman SW 50.1 rotor at 15 000 rpm for 10 min. The insoluble residue was digested with 1 mL 88% formic acid at 90°C for 15 min.A portion of the supernatant, which contained dissociativel...

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Section: Studies Of [35s]-labeled Proteoglycans Twenty 25-d-old Malementioning

confidence: 99%

Section: Studies Of [35s]-labeled Proteoglycans Twenty 25-d-old Malementioning

confidence: 99%

mentioning

confidence: 97%

mentioning

confidence: 99%

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Kinetics of Proteoglycans and Cells in Growth Plate of Normal, Diabetic, and Malnourished Rats

et al. 1990

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“…The full functional implications of these biochemical changes are at present unclear, but heparan sulphate alterations may hamper normal kidney performance [4], and a disturbed production of chondroitin sulphate proteoglycans may alter chondrocyte function [5]. It is also conceivable that maternal diabetes may induce proteoglycan disturbances in the offspring and thereby affect the maturation of chondrocytes leading to alterations of the cartilage model of the future osseous skeleton [6][7][8][9].…”

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confidence: 99%

Regionally disturbed production of cartilage proteoglycans in malformed fetuses from diabetic rats

Unger

Eriksson

1992

Diabetologia

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Summary.Fetuses from normal and manifestly diabetic rats were obtained on pregnancy day 20. The fetuses from the diabetic rats were of normal or malformed morphology. Three tissue groups were dissected free; costal cartilage, the hard tissue of the rear, and of the frontal portion of the mandible. These tissues were maintained in vitro for 24 h during which time they were labelled with [35S]sulphate. After the culture period the tissues were extracted with guanidine HC1 and the resulting residues were further extracted with alkali. The culture medium was saved and its macromolecular content was compared to that of the extracts. The proteoglycans recovered in all extracts eluted at two distinct positions after chromatography on a Sepharose CL-2B column (peak I: K,v -0.4, and peak II: K,v -0.8), but the elution patterns were markedly different in extracts from various tissues. Thus, in rib cartilage, the majority of the labelled proteoglycans were located in peak I (-90%) with no difference between extracts of fetuses from normal and diabetic pregnancies. In extracts of mandibular cartilaginous tissue from normal rat offspring the peak I percentage (60-80 %) was lower than in the rib cartilage extracts. In the extracts from the frontal portion of malformed mandibles of fetuses of diabetic rats, the peak I percentage (35 + 21%) was the lowest of all recorded and the only one to significantly differ from the other percentages in its (the frontal mandible) group. The results show an association between a congenital malformation, micrognathia, and a disturbance in the production of chondroitin sulphate proteoglycans in the malformed region.

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The mineral and mechanical properties of bone in chronic experimental diabetes

Einhorn

Boskey

Gundberg

et al. 1988

Journal Orthopaedic Research

126

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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.

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Biosynthesis of rat growth plate proteoglycans in diabetes and malnutrition

Cited by 26 publications

References 26 publications

Kinetics of Proteoglycans and Cells in Growth Plate of Normal, Diabetic, and Malnourished Rats

Kinetics of Proteoglycans and Cells in Growth Plate of Normal, Diabetic, and Malnourished Rats

Regionally disturbed production of cartilage proteoglycans in malformed fetuses from diabetic rats

The mineral and mechanical properties of bone in chronic experimental diabetes

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