Effects of tenoxicam and aspirin on the metabolism of proteoglycans and hyaluronan in normal and osteoarthritic human articular cartilage

Manicourt, Daniel; Egeren, A Druetz-Van; Haazen, L.; Deuxchaisnes, C Nagant de

doi:10.1111/j.1476-5381.1994.tb17111.x

Cited by 17 publications

(10 citation statements)

References 19 publications

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“…On the other hand, as reported previously (Mankin et al, 1971) the median content of hexuronate, and thus of proteoglycan, was higher in the group with MOA than in the group with SOA (41.5 versus 31.5 mg mg 71 tissue dry weight, respectively, P50.0001). The group with MOA also had a higher content of HA (0.47 versus 0.83 mg mg 71 tissue dry weight, respectively; P50.0001) and this in close agreement with a previous report (Manicourt et al, 1994). This overall cartilage chemistry was not signi®cantly aected by standard culture conditions and treatment with the NSAIDs examined over the 72-h period of culture (results not shown).…”

Section: Biochemical Characterization Of Cartilage Explantssupporting

confidence: 80%

“…This dierential eect of NSAIDs on cartilage metabolism is most relevant to clinical practice since any drug, that suppresses proteoglycan synthesis and impairs the chondrocyte to repair its damaged extracellular matrix, could potentially accelerate the breakdown of the cartilage tissue. On the other hand, although HA plays a central structural role in the supramolecular organization of proteoglycan and, hence on the biomechanical properties of articular cartilage, the possible eects of NSAIDs on the metabolism of this glycosaminoglycan has so far focused little investigative attention (Manicourt et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

“…Digests of cartilage and media were aliquoted. Samples were subjected either to biochemical determinations or to ion-exchange chromatography on Econo-Pac Q cartridge as previously reported (Manicourt et al, 1994).…”

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confidence: 99%

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Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human cartilage

Blot

Marcelis

Devogelaer

et al. 2000

British J Pharmacology

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1 Since nonsteroidal anti-in¯ammatory drugs (NSAIDs) may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in the metabolism of newly synthesized proteoglycan and hyaluronan (HA) molecules produced by aceclofenac, diclofenac and meloxicam in human osteoarthritic (OA) cartilage. 2 Explants were sampled from the medial femoral condyle and were classi®ed by use of the Mankin's histological-histochemical grading system. Cartilage specimens exhibited moderate (M) OA in 20 subjects and had severe (S) OA in 20. 3 Cartilage explants were pulsed with [-3H]-glucosamine and chased in the absence or in the presence of 0.3 ± 3 mg ml 71 of either aceclofenac, diclofenac or meloxicam. After papain digestion, the labelled chondroitin sulphate ([-3H]-proteoglycans) and [-3H]-HA molecules present in the tissue and media were puri®ed by anion-exchange chromatography. 4 In cartilage with MOA and SOA, the metabolic balance of proteoglycan and HA was unaected by diclofenac. In contrast, and in a dose-dependent manner, aceclofenac and meloxicam both increased the synthesis of proteoglycans and HA in explants with MOA and SOA; these two NSAIDs also reduced signi®cantly the net loss of [-3H]-proteoglycans and [-3H]-HA molecules from cartilage explants. 5 The data obtained in short-term in vitro cultures indicate that, at the concentrations found in synovial¯uid, aceclofenac and meloxicam may exert a favourable eect on the overall metabolism of proteoglycans and HA in cartilage with MOA and SOA.

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Section: Biochemical Characterization Of Cartilage Explantssupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

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Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human cartilage

Blot

Marcelis

Devogelaer

et al. 2000

British J Pharmacology

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“…In both experimental and human osteoarthritis, the progressive reduction in the HA content of articular cartilage is believed to contribute to the apparent irreversibility of the disease process [49-51]. Because the loss of HA from cartilage explants occurs in spite of an up-regulation in HA biosynthesis [52,53], a likely explanation is that HA strands are being degraded at an accelerated rate by a hyaluronidase active at near neutral pH. On the other hand, PH-20 may be also responsible for the release of aggrecan ternary complexes made of aggrecans, link protein, and HA from cartilage matrix upon stimulation with retinoic acid, a process that persists when cartilage explants are bathed with AG3340 at concentrations that completely inhibit the collagenolytic activity present in explants as well as the enzymatic activity of both aggrecanase-1 and aggrecanase-2 [54].…”

Section: Discussionmentioning

confidence: 99%

Untitled

2005

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Hyaluronan (HA), an important component of connective tissues, is highly metabolically active, but the mechanisms involved in its catabolism are still largely unknown. We hypothesized that a protein similar to sperm PH-20, the only mammalian hyaluronidase known to be active at neutral pH, could be expressed in connective tissue cells. An mRNA transcript similar to that of PH-20 was found in chondrocytes, synoviocytes, and dermal fibroblasts, and its levels were enhanced upon stimulation with IL-1. In cell layers extracted with Triton X-100 -but not with octylglucoside -and in culture media, a polyclonal antipeptide anti-PH-20 antibody identified protein bands with a molecular weight similar to that of sperm PH-20 (60 to 65 kDa) and exhibiting a hyaluronidase activity at neutral pH. Further, upon stimulation with IL-1, the amounts of the neutral-active hyaluronidase increased in both cell layers and culture media. These findings contribute potential important new insights into the biology of connective tissues. It is likely that PH-20 facilitates cell-receptor-mediated uptake of HA, while overexpression or uncontrolled expression of the enzyme can cause great havoc to connective tissues: not only does HA fragmentation compromise the structural integrity of tissues, but also the HA fragments generated are highly angiogenic and are potent inducers of proinflammatory cytokines. On the other hand, the enzyme activity may account for the progressive depletion of HA seen in osteoarthritis cartilage, a depletion that is believed to play an important role in the apparent irreversibility of this disease process.

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“…The development of a new generation of NSAIDs has taken these concerns into account. Tiaprofenic acid, tenoxicam, and meloxicam exert minimal effects on net PG and GAG synthesis in normal and osteoarthritic human cartilage . In another study, aceclofenac and meloxicam increased the biosynthesis of 3 H‐glucosamine‐labeled PG and HA in a dose‐dependent manner in the cartilage of patients with moderate or severe osteoarthritis.…”

Section: Therapeutic Agents Affecting Gag Metabolismmentioning

confidence: 95%

Drug‐Mediated Regulation of Glycosaminoglycan Biosynthesis

Ghiselli¹

2016

Medicinal Research Reviews

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Glycosaminoglycans (GAGs) are a heterogeneous family of unbranched polysaccharides that exist in either a free state or attached to proteins and are found on the cell surface as well as in the extracellular matrix. GAGs play essential roles in cellular and tissue homeostasis, and their metabolism is altered in response to several pathological conditions. Despite strong experimental evidence supporting the function of GAGs in various diseases, little is known about the regulation of GAG biosynthesis via pharmacological intervention. In recent studies, the effects of several experimental drugs on GAG biosynthesis in animal models of disease were examined and key enzymes involved in GAG biosynthesis were found to be druggable. In addition to experimental small-molecule drugs that alter GAG biosynthesis, a number of clinically approved drugs modulate GAG metabolism, contributing to the therapeutic benefits associated with the use of these drugs. In this review article, we propose a classification scheme for drugs affecting GAG biosynthesis. Our goal is to present a rational approach to investigate the pharmacological regulation of these important biological molecules.

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Effects of tenoxicam and aspirin on the metabolism of proteoglycans and hyaluronan in normal and osteoarthritic human articular cartilage

Cited by 17 publications

References 19 publications

Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human cartilage

Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human cartilage

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Drug‐Mediated Regulation of Glycosaminoglycan Biosynthesis

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