Modulation of articular chondrocyte proliferation and anionic glycoconjugate synthesis by glucosamine (GlcN), N-acetyl GlcN (GlcNAc) GlcN sulfate salt (GlcN.S) and covalent glucosamine sulfates (GlcN-SO4)

Terry, Doris E.; Rees-Milton, Karen; Pruss, Cynthia M.; Hopwood, John J.; Carran, John; Anastassiades, Tassos

doi:10.1016/j.joca.2007.02.010

Cited by 15 publications

(12 citation statements)

References 30 publications

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“…However, the increase of the concentration to 10 m M AGA monomer showed a remarkable reduction ( P < 0.05). The results of MTT indicated that exposure to GlcN inhibited cells proliferation, which was consistent with those obtained by other research groups 17, 37. The inhibitory effect of the GlcN molecule was attributed to the unsubstituted amino group.…”

Section: Resultssupporting

confidence: 91%

Synthesis and characterization of glucosamine modified poly(ethylene glycol) hydrogels via photopolymerization

Wang

et al. 2012

J of Applied Polymer Sci

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This study presented the synthesis and characterization of glucosamine (GlcN) modified poly (ethylene glycol) (PEG) hydrogels. The chemical structure was characterized by Fourier transform infrared (FTIR) and proton nuclear magnetic resonance ( 1 H NMR) spectroscopy. The morphology of hydrogels was observed by scanning electron microscopy (SEM). The results indicated that GlcN was successfully incorporated into PEG hydrogel network. Moreover, the data of the swelling ratio showed that the ratio of GlcN-modified PEG hydrogels was lower than that of pure poly(ethylene glycol) diacrylated (PEGDA). Biocompatibility of unreacted GlcN monomer and GlcN-modified hydrogels was also evaluated in vitro. Compared with glucosamine hydrochloride, 2 and 5 mM N-acroloyl-glucosamine monomer exhibited no toxicity against bone marrow stromal cells (BMSCs), while with the concentration increased to 10 mM, cell viability appeared to decrease. However, when BMSCs were encapsulated in GlcN-modified hydrogels via photopolymerization method, cells remained vigorous viability. Metabolic activity of the encapsulated cells demonstrated GlcN-modified hydrogels was favorable for cell proliferation. Compared with free GlcN, covalent binding GlcN showed lower cytotoxicity and higher cell proliferation properties. As a result, GlcN-modified PEGDA hydrogels could be used as safe and injectable cell carriers for in situ tissue engineering applications.

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Section: Resultssupporting

confidence: 91%

Synthesis and characterization of glucosamine modified poly(ethylene glycol) hydrogels via photopolymerization

Wang

et al. 2012

J of Applied Polymer Sci

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“…Specifically, prolonged exposure of primary chondrocytes to optimal concentrations of GlcN increased matrix production with concomitant inhibition of chondrocyte proliferation [46]. The GlcN concentration significantly affected cell behavior and adding GlcN led to a concentration-dependent decrease in bovine articular cartilage proliferation in hydrogel [46,47]. …”

Section: Resultsmentioning

confidence: 99%

Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for Cartilage Tissue Engineering

Chen

Kuo

Wang

et al. 2016

IJMS

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Glucosamine (GlcN) fulfills many of the requirements as an ideal component in scaffolds used in cartilage tissue engineering. The incorporation of GlcN in a gelatin/hyaluronic acid (GH) cryogel scaffold could provide biological cues in maintaining the phenotype of chondrocytes. Nonetheless, substituting gelatin with GlcN may also decrease the crosslinking density and modulate the mechanical properties of the cryogel scaffold, which may be beneficial as physical cues for chondrocytes in the scaffold. Thus, we prepared cryogel scaffolds containing 9% GlcN (GH-GlcN9) and 16% GlcN (GH-GlcN16) by carbodiimide-mediated crosslinking reactions at −16 °C. The crosslinking density and the mechanical properties of the cryogel matrix could be tuned by adjusting the content of GlcN used during cryogel preparation. In general, incorporation of GlcN did not influence scaffold pore size and ultimate compressive strain but increased porosity. The GH-GlcN16 cryogel showed the highest swelling ratio and degradation rate in hyaluronidase and collagenase solutions. On the contrary, the Young’s modulus, storage modulus, ultimate compressive stress, energy dissipation level, and rate of stress relaxation decreased by increasing the GlcN content in the cryogel. The release of GlcN from the scaffolds in the culture medium of chondrocytes could be sustained for 21 days for GH-GlcN16 in contrast to only 7 days for GH-GlcN9. In vitro cell culture experiments using rabbit articular chondrocytes revealed that GlcN incorporation affected cell proliferation, morphology, and maintenance of chondrogenic phenotype. Overall, GH-GlcN16 showed the best performance in maintaining chondrogenic phenotype with reduced cell proliferation rate but enhanced glycosaminoglycans (GAGs) and type II collagen (COL II) secretion. Quantitative real-time polymerase chain reaction also showed time-dependent up-regulation of cartilage-specific marker genes (COL II, aggrecan and Sox9) for GH-GlcN16. Implantation of chondrocytes/GH-GlcN16 constructs into full-thickness articular cartilage defects of rabbits could regenerate neocartilage with positive staining for GAGs and COL II. The GH-GlcN16 cryogel will be suitable as a scaffold for the treatment of articular cartilage defects.

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“…Increased aggrecan and procollagen α 1 (II) expression has been observed with 2 mM glucosamine compared with 0.7 µM, whereas 15 mM glucosamine is inhibitory (Varghese et al 2007). On the other hand, the inhibition of PG synthesis in the presence of glucosamine has been also reported (de Mattei et al 2002;Uitterlinden et al 2006;Terry et al 2007). Cell and explant cultures might thus behave differently.…”

Section: Discussionmentioning

confidence: 87%

Glucosamine sulphate does not increase extracellular matrix production at low oxygen tension

Pöytäkangas

Jauhiainen

et al. 2009

Cell Tissue Res

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Low oxygen tension may change the dependence of chondrocytes on exogenous carbohydrate sources. In this study, we have investigated whether glucosamine sulphate (GS) stimulates proteoglycan synthesis, the mRNA expression of aggrecan and of type II collagen, and UDP-sugar levels in bovine primary chondrocytes under a low oxygen (O(2)) atmosphere. Chondrocytes from bovine femoral condyles were cultivated with or without GS or sulphate at various concentrations in low- (5.5 mM) or high-glucose (25 mM) DMEM under either a 5% or 20% O(2) atmosphere for 2 or 8 days after isolation. The mRNA expression of aggrecan and type II collagen and the synthesis of glycosaminoglycan (GAG) were determined by quantitative real-time reverse transcription with polymerase chain reaction and a [(35)S]-sulphate incorporation assay, respectively. Aggrecan promoter activity was analysed by a dual-luciferase reporter gene assay. Intracellular UDP-N-acetylhexosamines (UDP-HexN), UDP-glucuronic acid and UDP-hexoses were analysed by reversed-phase high-performance liquid chromatography electrospray ionization mass spectrometry. A low (5%) O(2) atmosphere significantly increased GAG synthesis, mRNA expression of aggrecan and of type II collagen and aggrecan promoter activity in bovine primary chondrocytes. A high (1 mM) concentration of GS was required to increase the level of UDP-HexN. However, GS did not increase GAG synthesis, aggrecan promoter activity or mRNA expression of aggrecan and of type II collagen. Interestingly, a 5% O(2) atmosphere increased the level of UDP-HexN in 8-day cultures without GS treatment. Thus, exogenous GS does not change chondrocyte metabolism, whereas a 5% O(2) atmosphere stimulates extracellular matrix production in bovine primary chondrocytes. The balance of UDP-sugars is changed under a 5% O(2) atmosphere for longer culture periods.

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Modulation of articular chondrocyte proliferation and anionic glycoconjugate synthesis by glucosamine (GlcN), N-acetyl GlcN (GlcNAc) GlcN sulfate salt (GlcN.S) and covalent glucosamine sulfates (GlcN-SO4)

Cited by 15 publications

References 30 publications

Synthesis and characterization of glucosamine modified poly(ethylene glycol) hydrogels via photopolymerization

Synthesis and characterization of glucosamine modified poly(ethylene glycol) hydrogels via photopolymerization

Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for Cartilage Tissue Engineering

Glucosamine sulphate does not increase extracellular matrix production at low oxygen tension

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