Binding of haptoglobin, inter-alpha-trypsin inhibitor, and alpha 1 proteinase inhibitor to synovial fluid hyaluronate and the influence of these proteins on its degradation by oxygen derived free radicals.

Hutadilok, Nongporn; Ghosh, Peter; Brooks, Peter

doi:10.1136/ard.47.5.377

Cited by 64 publications

(41 citation statements)

References 32 publications

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“…Our results were in agreement with the observation and further indicated that the SHAP-HA complex itself was enough to form the aggregates, which implies an interesting role for SHAP in the regulation of HA aggregation. Such a role is apparently distinct from the previously described one, which showed that the formation of protein-HA complexes helps protect the cartilage proteoglycan-HA aggregates from disruption by oxygen-derived free radicals and hydrogen peroxide (28,29).…”

Section: Discussionmentioning

confidence: 55%

Molecular Heterogeneity of the SHAP-Hyaluronan Complex

Yingsung

Zhuo

Mörgelin

et al. 2003

Journal of Biological Chemistry

102

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We previously found that a covalent complex of SHAPs (serum-derived hyaluronan-associated proteins), the heavy chains of inter-␣-trypsin inhibitor family molecules, with hyaluronan (HA) is accumulated in synovial fluid of patients with rheumatoid arthritis, and the complex is circulated in patient plasma at high concentrations. How the SHAP-HA complex participates in this disease is unknown. To address this question, it is essential to clarify the structural features of this macromolecule. The SHAP-HA complex purified from synovial fluid of the patients by three sequential CsCl isopycnic centrifugations was heterogeneous in density, and the fractions with different densities had distinct SHAPto-HA ratios. Agarose gel electrophoresis and column chromatography revealed that there was no apparent difference in the size distribution of HA to which SHAPs were bound between the fractions with different densities. The SHAP-HA complex in the higher density fraction had fewer SHAP molecules per HA chain. Therefore, the difference between the fractions with different densities was due to a heterogeneous population of the SHAP-HA complex, namely the different number of SHAP molecules bound to an HA chain. Based on the SHAP and HA contents of the purified preparations, we estimated that an HA chain with a molecular weight of 2 ؋ 10 6 has as many as five covalently bound SHAPs, which could give a proteinaceous multivalency to HA. Furthermore, we also found that the SHAP-HA complex tends to form aggregates, judging from the migration and elution profiles in agarose gel electrophoresis and gel filtration, respectively. The multivalent feature of the SHAP-HA complex was also confirmed by the negative staining electron micrographic images of the purified fractions. Taken together, those structural characteristics may underlie the aggregate-forming and extracellular matrix-stabilizing ability of the SHAP-HA complex.

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Section: Discussionmentioning

confidence: 55%

Molecular Heterogeneity of the SHAP-Hyaluronan Complex

Yingsung

Zhuo

Mörgelin

et al. 2003

Journal of Biological Chemistry

102

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“…Remodeling of the extracellular matrix is a critical event in normal processes such as tissue morphogenesis, differentiation, and wound healing; inter-␣-trypsin inhibitors are believed to participate in these events. These glycoproteins are also involved in pathological conditions such as tumor invasion (6), metastasis (7), and arthritis (8), which reinforces the interest in understanding their regulation.…”

mentioning

confidence: 76%

Human Inter-α-Trypsin Inhibitor Heavy Chain H3 Gene

Diarra‐Mehrpour

Sarafan

Bourguignon

et al. 1998

Journal of Biological Chemistry

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“…44 Other potential mechanisms of cytokine regulation of HA include catabolism mediated by HA-degrading hyaluronidases, 45 cellular trafficking of HAS proteins, activation of sugar nucleotide HA building blocks, interactions between HAS enzymes and the nascent growing HA chains as they are extruded from the cell, 46,47 and interactions between HA and binding proteins such as 18 that stabilize HA and prevent its depolymerization in SF. 48 Signaling mechanisms behind PRG4 regulation have been studied less extensively than that of HA, but have suggested the role of Smad2=3 in mediating TGF-b1 signaling. 49 Although these regulatory mechanisms of HA and PRG4 secretion by individual cytokines have been identified, it is unknown whether regulation by cytokines in combination occurs through signaling pathways that are distinct or involve crosstalk.…”

Section: Discussionmentioning

confidence: 99%

Interactive Cytokine Regulation of Synoviocyte Lubricant Secretion

Blewis

Lao

Schumacher

et al. 2010

Tissue Engineering Part A

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Cytokine regulation of synovial fluid (SF) lubricants, hyaluronan (HA), and proteoglycan 4 (PRG4) is important in health, injury, and disease of synovial joints, and may also provide powerful regulation of lubricant secretion in bioreactors for articulating tissues. This study assessed lubricant secretion rates by human synoviocytes and the molecular weight (MW) of secreted lubricants in response to interleukin (IL)-1b, IL-17, IL-32, transforming growth factor-beta 1 (TGF-b1), and tumor necrosis factor-alpha (TNF-a), applied individually and in all combinations. Lubricant secretion rates were assessed using ELISA and binding assays, and lubricant MW was assessed using gel electrophoresis and Western blotting. HA secretion rates were increased *40-fold by IL-1b, and increased synergistically to *80-fold by the combination of IL-1b þ TGF-b1 or TNF-a þ IL-17. PRG4 secretion rates were increased *80-fold by TGF-b1, and this effect was counterbalanced by IL-1b and TNF-a. HA MW was predominantly <1 MDa for controls and individual cytokine stimulation, but was concentrated at >3 MDa after stimulation by IL-1b þ TGF-b1 þ TNF-a to resemble the distribution in human SF. PRG4 MW was unaffected by cytokines and similar to that in human SF. These results contribute to an understanding of the relationship between SF cytokine and lubricant content in health, injury, and disease, and provide approaches for using cytokines to modulate lubricant secretion rates and MW to help achieve desired lubricant composition of fluid in bioreactors.

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Binding of haptoglobin, inter-alpha-trypsin inhibitor, and alpha 1 proteinase inhibitor to synovial fluid hyaluronate and the influence of these proteins on its degradation by oxygen derived free radicals.

Cited by 64 publications

References 32 publications

Molecular Heterogeneity of the SHAP-Hyaluronan Complex

Molecular Heterogeneity of the SHAP-Hyaluronan Complex

Human Inter-α-Trypsin Inhibitor Heavy Chain H3 Gene

Interactive Cytokine Regulation of Synoviocyte Lubricant Secretion

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