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Biomedical subjects

Jeremiah E Silbert

Publications and source records attributed to Jeremiah E Silbert.

6 recordsLinked to original sources
PubMed2005

Fasting serum sulfate levels before and after development of osteoarthritis in participants of the veterans administration normative aging longitudinal study do not differ from levels in participants in whom osteoarthritis did not develop.

OBJECTIVE: To determine whether the development of osteoarthritis (OA) in men over a 33-year period is related to lower sulfate levels in stored serum collected during that time interval. METHODS: Stored serum samples from participants in the Veterans Administration Normative Aging Study were assayed for sulfate by ion-exchange chromatography. Samples had been obtained every 3-5 years during part or all of a 33-year portion of the study. Sulfate levels were determined in serum from all participants who underwent knee replacement surgery and had evidence of radiographic hand OA, from some of the participants who had evidence of radiographic hand OA but had not undergone knee replacement surgery, from all participants who underwent knee replacement surgery but had no evidence of radiographic hand OA, and from age-matched participants who had no evidence of OA by history, physical examination, or hand radiography. RESULTS: Serum sulfate levels in participants, with or without radiographic hand OA and/or knee replacements, who were ages 34-72 years at the first examination, ranged from 0.21 mM to 0.51 mM over the course of a maximum of 33 years. Both the overall mean and median sulfate levels rose from 0.32 mM at age 40-50 years to 0.38 mM at age 70-80 years, and the overall mean and median for all ages was 0.36 mM. There were no significant differences in sulfate levels between subjects in any of the 4 groups. CONCLUSION: There was no evidence of a relationship between these serum sulfate levels and the development of OA. However, all samples were collected after overnight fasting, and no participant was younger than age 34 years at the initiation of the study. It remains to be determined whether differences in the time of ingestion of daily dietary protein providing sulfate are related to the development of OA, or whether sulfate levels measured at an earlier age could be a factor.

Adult↗
PubMed2004

Use of 3H-glucosamine and 35S-sulfate with cultured human chondrocytes to determine the effect of glucosamine concentration on formation of chondroitin sulfate.

OBJECTIVE: To determine whether addition of glucosamine will stimulate synthesis of chondroitin sulfate by cultures of human chondrocytes, and to compare the relative contribution of endogenous glucosamine to exogenous glucosamine in forming chondroitin sulfate. METHODS: Cultured human chondrocytes were incubated with (35)S-sulfate and various amounts of glucosamine to determine whether any incremental formation of chondroitin (35)S-sulfate occurred. Similarly, chondrocytes incubated with variable concentrations of (3)H-glucosamine were examined to determine how much the incorporation into (3)H-chondroitin sulfate was diluted by provision of endogenous glucosamine that was derived by metabolism from glucose. RESULTS: No stimulation of chondroitin (35)S-sulfate synthesis was found at concentrations of glucosamine up to 1 mM, a concentration of (3)H-glucosamine well above the concentrations that could be presented to cartilage after ingestion of advertised amounts of glucosamine. Furthermore, there was significant dilution of exogenous glucosamine by endogenous glucosamine provided by metabolism from glucose. CONCLUSION: The results indicate that exogenous glucosamine does not stimulate chondroitin sulfate synthesis by human chondrocytes. Furthermore, the cells have the capacity to form amounts of glucosamine from glucose far in excess of that provided from exogenous sources, except at concentrations greater than could possibly be achieved with oral administration of glucosamine.

Cell Line, Transformed↗
PubMed2003

Effects of [3H]glucosamine concentration on [3H]chondroitin sulphate formation by cultured chondrocytes.

GlcN (glucosamine) is now promoted over the counter for implied treatment of osteoarthritis, ostensibly by stimulating biosynthesis of cartilage chondroitin sulphate. In order to evaluate whether exogenous GlcN has any stimulatory effect, we have incubated mouse chondrocytes with [(35)S]sulphate and various amounts of GlcN, to determine whether any increment in chondroitin [(35)S]sulphate formation occurs. Similarly we have used varying concentrations of [(3)H]GlcN to determine the dilution of incorporation into [(3)H]chondroitin sulphate due to provision of endogenous GlcN by metabolism from glucose at two different glucose concentrations. The incorporation of both (35)S and (3)H was essentially linear over a 5 h time period. We found no stimulation of chondroitin [(35)S]sulphate synthesis at lower concentrations of GlcN, and a significant reduction at higher concentrations. Even at concentrations of [(3)H]GlcN that were greater than could be achieved with standard doses of oral GlcN, there was significant dilution of exogenous GlcN. Furthermore, an artificial acceptor for glycosaminoglycan synthesis in cell culture, 4-methylumbelliferyl beta-D-xyloside, did not modify the provision of GlcN from endogenous sources, even though it stimulated chondroitin sulphate synthesis 4 -5-fold at each GlcN concentration. We conclude that the cells have excess capacity to form maximal amounts of GlcN from glucose so that exogenous GlcN does not stimulate chondroitin sulphate synthesis.

Animals↗
PubMed2002

Biosynthesis of chondroitin/dermatan sulfate.

Chondroitin sulfate and dermatan sulfate are synthesized as galactosaminoglycan polymers containing N-acetylgalactosmine alternating with glucuronic acid. The sugar residues are sulfated to varying degrees and positions depending upon the tissue sources and varying conditions of formation. Epimerization of any of the glucuronic acid residues to iduronic acid at the polymer level constitutes the formation of dermatan sulfate. Chondroitin/dermatan glycosaminoglycans are covalently attached by a common tetrasaccharide sequence to the serine residues of core proteins while they are adherent to the inner surface of endoplasmic reticulum/Golgi vesicles. Addition of the first sugar residue, xylose, to core proteins begins in the endoplasmic reticulum, followed by the addition of two galactose residues by two distinct glycosyl transferases in the early cis/medial regions of the Golgi. The linkage tetrasaccharide is completed in the medial/trans Golgi by the addition of the first glucuronic acid residue, followed by transfer of N-acetylgalactosamine to initiate the formation of a galactosaminoglycan rather than a glucosaminoglycan. This specific N-acetylgalactosaminyl transferase is different from the chondroitin synthase involved in generation of the repeating disaccharide units to form the chondroitin polymer. Sulfation of the chondroitin polymer by specific sulfotransferases occurs as the polymer is being formed. All the enzymes in the pathway for synthesis have been cloned, with the exception of the glucuronyl to iduronyl epimerase involved in the formation of dermatan residues.

Animals↗
PubMed2002

Proteoglycans synthesized by canine intervertebral disc cells grown in a type I collagen-glycosaminoglycan matrix.

The objective of this study was to determine the characteristics of proteoglycans synthesized by canine annulus fibrosus cells expanded in number in monolayer culture through passage 4 and subsequently grown in a type I collagen-glycosaminoglycan matrix to be employed for tissue engineering. Newly synthesized [35S]sulfate-labeled proteoglycans were analyzed by gel chromatography, including sequential digestion with enzymes and nitrous acid. After 1 week in culture, the percentage of cell-associated, aggregated proteoglycans synthesized in type I collagen-glycosaminoglycan matrices was 52% compared with 38% by the cells in monolayer. The percentage of aggregated proteoglycan in each group increased only slightly with the addition of exogenous hyaluronic acid, but remained significantly different from each other. There were at least three different hydrodynamic sizes of proteoglycans both in the collagen-glycosaminoglycan matrix and in monolayer; the average size was larger in the collagen matrices and the glycosaminoglycan chains were longer. The proteoglycans contained chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate. The results provide a foundation for future investigations of collagen-glycosaminoglycan matrices for intervertebral disc tissue engineering.

Animals↗