Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants

Abstract

The effects of GlcN on gene expression in a human osteoarthritic explant model suggest that enzymatic breakdown of the extra-cellular matrix might be reduced by the addition of 5mM GlcN. Additionally, restoration of already damaged cartilage is not to be expected, because gene expression of anabolic genes is also down-regulated. We suggest that chondroprotective properties of GlcN in vivo may be based on inhibiting further degradation due to catabolic activities, rather than on the ability to rebuild cartilage.

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

“…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.…”

Matrix metalloproteinase and aggrecanase generated aggrecan fragments: implications for the diagnostics and therapeutics of destructive joint diseases

“…Xiang et al [2006] identified highly potent compounds against ADAMTS-4 consisting of biphenylsulfonamidocarboxilic acid with nanomolar antagonist activity one of which demonstrated an 89% suppression of proteoglycan destruction. Different variants of glucosamine can block ADAMTS-5 mediated aggrecan degradation ex vivo in human osteoarthritic explants, though with millimolar activity [Uitterlinden et al, 2006]. Finally, the selective aggrecanase inhibitor, SB-703704, exhibited efficient suppression of ADAMTS-4 mediated 374 ARGSVI neoepitope formation both in in vitro test-tube digestion experiments, as well as in IL-1a-treated human OA cartilage explants .…”

“…However, several problems have been observed when testing them in clinical trials such as rapid metabolization with poor pharmacokinetics after oral treatment with loss of in vivo activity before reaching and penetrating into the articular cartilage [Yu et al, 1997;Close, 2001]. Non-peptidyl agents include BAY-12-9566, the tetracycline-derived antibiotics anthracycline and doxycycline, minocycline, biphosphonates, different analogs of glucosamine, XS309, GM6001 (galardin), and the compounds forskolin and isobutylmethylxanthine (IBMX) [Kloppenburg et al, 1995;Malemud et al, 1996;Arner et al, 1999;Hidalgo and Eckhardt, 2001;Uitterlinden et al, 2006]. In this regard, forskolin and IBMX are interesting as they exhibit a dose-dependent increase on intracellular cAMP levels in isolated bovine chondrocytes, an effect associated with decreased levels of MMPs and increased synthesis of proteoglycans [Malemud et al, 1996.…”

Topical Issues of Osteoarthritis Treatment in Clinical Practice

“…Особенно значимым является ее способность оказывать противовоспалительное действие, обусловленное блоки-рованием синтеза супероксидных радикалов макрофага-ми и лизосомальных ферментов [3,5,32,34]. Поскольку сульфаты участвуют в синтезе глюкозаминогликанов (ГГ) и метаболизме ткани хряща, сульфатные эфиры боковых цепей в составе протеогликанов имеют большое значе-ние для поддержания эластичности и способности удер-живать воду матриксом хряща.…”

“…Показаниями для назначения являются первичный и вторичный остеоартроз, в том числе коленного, тазобе-дренного суставов, и спондилоартроз [6,8,14,25,27,29,32].…”