Hyaluronic acid in human synovial effusions; A sensitive indicator of altered connective tissue cell function during inflammation

Castor, C. William; Prince, Robert K.; Hazelton, Margaret J.

doi:10.1002/art.1780090606

Cited by 49 publications

(17 citation statements)

References 12 publications

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“…The importance of Golgi apparatus in synthesis of acid mucopolysaccharides in synovial cells (Roy and Ghadially, 1967) and in chondrocytes (Godman and Lane, 1964) (Decker, McGuckin, McKenzie, and Slocumb, 1959;Castor, Prince, and Hazelton, 1966 (Barnett, Davies, and MacConaill, 1961).…”

Section: Golgi Apparatusmentioning

confidence: 99%

Ultrastructure of synovial membrane in osteo-arthritis.

Roy¹

1967

Annals of the Rheumatic Diseases

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Section: Golgi Apparatusmentioning

confidence: 99%

Ultrastructure of synovial membrane in osteo-arthritis.

Roy¹

1967

Annals of the Rheumatic Diseases

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“…In addition, as has been demonstrated many times, degradation products of HA possess a series of unwanted properties such as acting as chemoattractants, inducing blood vessel growth, as well as activating and inducing the release of proinflammatory molecules in leukocytes and endothelial cells (10 -15). That detection of increased levels of HA in human synovium effusion serves as a sensitive indicator of altered connective tissue cell function has been recognized for some time (16). Furthermore, while in healthy joints only a fine layer of HA covers and protects joint surfaces, RA is characterized by uncontrolled HA production, often leading to enormous amounts of HA in affected joints.…”

mentioning

confidence: 99%

Effects of Leflunomide on Hyaluronan Synthases (HAS): NF-κB-Independent Suppression of IL-1-Induced HAS1 Transcription by Leflunomide

Stuhlmeier¹

2005

The Journal of Immunology

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Despite evidence that points to unfettered hyaluronic acid (HA) production as a culprit in the progression of rheumatic disorders, little is known about differences in regulation and biological functions of the three hyaluronan synthase (HAS) genes. Testing the effects of drugs with proven anti-inflammatory effects could help to clarify biological functions of these genes. In this study, we demonstrate that leflunomide suppresses HA release in fibroblast-like synoviocytes (FLS) in a dose-dependent manner. We further demonstrate that leflunomide suppresses HA synthase activity, as determined by 14C-glucuronic acid incorporation assays. Additional experiments revealed that in FLS, leflunomide specifically blocked the induction of HAS1. HAS2 and HAS3, genes that are, in contrast to HAS1, constitutively expressed in FLS, are not significantly affected. Leflunomide can function as a NF-κB inhibitor. However, EMSA experiments demonstrate that at the concentrations used, leflunomide neither interferes with IL-1β- nor with PMA-induced NF-κB translocation. Furthermore, reconstituting the pyrimidine synthase pathway did not lead to the restoration of IL-1β-induced HAS1 activation. More importantly, two tyrosine kinase inhibitors mimicked the effect of leflunomide in that both blocked IL-1β-induced HAS1 activation without affecting HAS2 or HAS3. These data point at HAS1 activation as the possible cause for unfettered HA production in rheumatoid arthritis and might explain, at least in part, the beneficial effects of leflunomide treatment. These findings also support the concept that IL-1β-induced HAS1 activation depends on the activation of tyrosine kinases, and indicate that leflunomide blocks HA release by suppressing tyrosine kinases rather than through inhibition of NF-κB translocation.

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“…The concentration of hyaluronic acid in rabbit pericardial liquid has been found to be 82 µg/mL [39], and that in pleural liquid~1 µg/mL [16]. Both concentrations are much smaller than that required to bring µ back to its control value after mesothelial blotting and of that found in the synovial fluid (1-4 mg/mL; [41]), where the role of hyaluronan as a lubricant is important. Hence, even though hyaluronic acid acts as a good lubricant when applied to damaged mesothelium, its role as a lubricant of mesothelial surfaces under physiological conditions is not demonstrated.…”

Section: Hyaluronan Lubricant Effectsmentioning

confidence: 95%

Pleural Lubrication

et al. 2016

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During breathing, the pleural surfaces slide against each other continuously without damage. Pleural liquid and lubricating molecules should provide the lubrication of the sliding surfaces, thus protecting the mesothelium from shear-induced abrasion. D' Angelo et al. (Respir. Physiol. Neurobiol. 2004) measured the coefficient of kinetic friction (µ) of rabbit parietal pleura sliding against visceral pleura in vitro at physiological velocities and under physiological loads; it was~0.02 and did not change with sliding velocity, consistent with boundary lubrication. µ in boundary lubrication can be influenced by surface molecules like hyaluronan, sialomucin or surface active phospholipidis. Hyaluronan or sialomucin is able to restore good boundary lubrication in damaged mesothelium. Nevertheless, hyaluronidase and neuraminidase treatment of the mesothelium does not increase µ, though neuraminidase cleaves sialic acid from the mesothelium. Short pronase or phospholipase treatment, so as to affect only the mesothelial glycocalyx, increases µ, and this increase is removed by hyaluronan or sialomucin. On the other hand, addition of phospholipids after phospholipase treatment produces a small effect relative to that of hyaluronan or sialomucin, and this effect is similar with unsaturated or saturated phospholipids. In damaged mesothelium, the lubrication regimen becomes mixed, but addition of hyaluronan or sialomucin restores boundary lubrication.

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Hyaluronic acid in human synovial effusions; A sensitive indicator of altered connective tissue cell function during inflammation

Cited by 49 publications

References 12 publications

Ultrastructure of synovial membrane in osteo-arthritis.

Ultrastructure of synovial membrane in osteo-arthritis.

Effects of Leflunomide on Hyaluronan Synthases (HAS): NF-κB-Independent Suppression of IL-1-Induced HAS1 Transcription by Leflunomide

Pleural Lubrication

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