Advances in Chondroitin Sulfate Analysis: Application in Physiological and Pathological States of Connective Tissue and During Pharmacological Treatment of Osteoarthritis

Abstract

Recent glycobiology studies have suggested fundamental biological functions for chondroitin sulfate (CS) and dermatan sulfate (DS), which are widely distributed as glycosaminoglycans (GAGs) sidechains of proteoglycans (PGs) in the extracellular matrix and at cellular level. Several biological functions are closely associated with the structure and in particular with the sulfation patterns of these polysaccharides. CS is also used as a structure-modifying osteoarthritis (OA) drug that reverses, retards, or stabilizes the pathology of OA, thereby providing symptomatic relief in the long-term treatment. Advances in analytical separational techniques, including agarose-gel electrophoresis, high-performance liquid chromatography (HPLC), capillary electrophoresis (HPCE), fluorophore-assisted carbohydrate electrophoresis (FACE) and electrospray ionization mass (ESI-MS) enable us to examine alterations of CS/DS with respect to their quantities and fine structural features in various pathological conditions, thus becoming applicable for diagnosis. Furthermore, sensitive analytical procedures enable us to follow the pharmacological application of CS in the treatment of OA and to monitor the progression of the disorder. In this review, the chromatographic and electromigration procedures developed to analyse and characterise CS/DS are presented. Moreover, a critical evaluation of the biological relevance of the results obtained by the developed methodology is discussed.

Quality of different chondroitin sulfate preparations in relation to their therapeutic activity

“…[25] It is well known that specific activity depends on the chondroitin sulfate structure and properties. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Additionally, chondroitin is administered orally during therapy and bioavailability and pharmacokinetic parameters have been reported to change depending on its structural characteristics and origin. [38][39][40] As a consequence, chondroitin sulfate with a low quality of content and properties, generally present in nutraceuticals, would be unable to exert comparable pharmacological effects to those of the pharmaceutical-grade chondroitin sulfate, and the same clinical effects would not be produced unless various chondroitin sulfate preparations have a similar structure.…”

“…[1] Biological role of chondroitin sulfate Recent evidence from glycobiology studies suggests that proteoglycans, and their complex polysaccharidic macromolecules, are not only structural components, but they also participate in and regulate many cellular events and physiological processes. [1,2] Growing recent evidence suggests that chondroitin sulfate (and dermatan sulfate) chains have intriguing functions in central nervous system development, wound repair, infection, growth factor signalling, morphogenes and cell division, differentiation and migration, in addition to osteoarthritis (OA; see below) and their conventional structural roles (for more complete and specialized papers see references [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] ).…”

The xylosyltransferase Ι gene polymorphism c.343G>T (p.A115S) is associated with decreased serum glycosaminoglycan levels

“…Truncation to less than 214 amino acids resulted in impaired or abolished retention of XT-I constructs in the Golgi apparatus, showing the importance of the stem region for the proper localization [3]. Changes in GAG content and distribution are believed to play an important role in the development of many diseases such as arthritis, atherosclerosis, cancer, diabetes, Graves' disease, interstitial cystitis and osteoarthritis [4][5][6][7][8][9]. For example, an elevated serum total GAG concentration in type 2 diabetic patients was found to be positively influenced by poor metabolic compensation of diabetes and the presence of vascular complications [6].…”

Chondroitin C lyase [4.2.2.] is unable to cleave fructosylated sequences inside the partially fructosylated Escherichia coli K4 polymer

“…Moreover, fructose residues may be removed by hydrolytic treatment in acidic conditions [1,4,5] to produce a chondroitin backbone useful to gain detailed insight into the mode of action of several enzymes [6,7]. Furthermore, bacterial polysaccharide lyases presumably play a role in the initial catabolism of GAGs [8], and they have found many applications, including the preparation of new therapeutic agents from natural GAGs [9], the analysis of GAGs found in tissues and biological fluids [10,11], and the removal of GAGs from the circulation [12]. Finally, due to their highly specific action, these enzymes are potentially useful tools for structural studies of complex polysaccharides [8,13].…”