Expression and Significance of MMPs in Synovial Fluid, Serum and PBMC Culture Supernatant Stimulated by LPS in Osteoarthritis Patients With or Without Diabetes

Luo, Simin; Shi, Qiankun; Chen, Jun-Yuan; Wang, Huajun; Wu, Wenrui; Zha, Zhengang

doi:10.1055/s-0043-122223

Cited by 20 publications

(12 citation statements)

References 39 publications

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“…7,8 Some of these MMPs have been shown to be upregulated by inflammatory cytokines or mononuclear cells. 9,10 It has also been shown that synovitis upregulates MMP expression and therefore perpetuates the degradation characteristic of progressive OA. 11 Normally MMPs are regulated in tissues by tissue inhibitors of metalloproteinases (TIMPs).…”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinases and Their Inhibitors and Proteoglycan 4 in Patients Undergoing Total Joint Arthroplasty

Thorson

Galicia

Burleson

et al. 2019

Clin Appl Thromb Hemost

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Osteoarthritis, a degenerative disease of the joints, is the most common form of arthritis in the knee. Total joint arthoplasty is a commonly used treatment for joint degeneration and osteoarthritis, and due to these factors, TJA for hip and knee joints is projected to grow by 137% and 601% between 2005 and 2030. Matrix metalloproteases are enzymes found in the extracellular matrix that cleave matrix components. Normally MMPs are downregulated in tissues by Tissue Inhibitors of Metalloproteases, or TIMPs. The relative concentration of TIMPs also may denote some of the activity of the MMPs found in serum. Lubricin (proteoglycan 4) is a molecule found in the synovial fluid that protects joints by dissipating strain energy during locomotion. Lubricin synovial fluid concentration is also diminished in many patients with osteoarthritis, but not all. Given the importance of these three sets of molecules, our lab investigated the correlation between circulating lubricin, MMP levels and TIMPs levels. Blood plasma samples were obtained from de-identified subjects undergoing total joint arthroplasty at Loyola University Medical Center and the University of Utah. Normal blood plasma from pooled healthy individuals served as a control. We analyzed biomarker levels in plasma using ELISA. Our data show that MMP-1 and 9 were increased in TJA patients compared to normal controls, while MMP-2 and 13 were decreased. We also found decreased lubricin and tissue factor in surgical patients relative to controls. These data support the idea that lubricin is vital in protecting the synovial joint and that MMPs play a complex role in the destruction of the joint.

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Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinases and Their Inhibitors and Proteoglycan 4 in Patients Undergoing Total Joint Arthroplasty

Thorson

Galicia

Burleson

et al. 2019

Clin Appl Thromb Hemost

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“…High molecular weight HA also has anti-inflammatory properties [130]; its localisation at the cartilage surface contributes to joint lubrication. Lubricin in the surface regions of cartilage also binds to a number of cartilage proteins [131] contributing to joint lubrication, and the retention of lubricin at the cartilage surface [132] and may promote cartilage regeneration [133,134,135].…”

Section: Discussionmentioning

confidence: 99%

A Retrospective Analysis of the Cartilage Kunitz Protease Inhibitory Proteins Identifies These as Members of the Inter-α-Trypsin Inhibitor Superfamily with Potential Roles in the Protection of the Articulatory Surface

Smith

Melrose

2019

IJMS

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Aim: The aim of this study was to assess if the ovine articular cartilage serine proteinase inhibitors (SPIs) were related to the Kunitz inter-α-trypsin inhibitor (ITI) family. Methods: Ovine articular cartilage was finely diced and extracted in 6 M urea and SPIs isolated by sequential anion exchange, HA affinity and Sephadex G100 gel permeation chromatography. Selected samples were also subjected to chymotrypsin and concanavalin-A affinity chromatography. Eluant fractions from these isolation steps were monitored for protein and trypsin inhibitory activity. Inhibitory fractions were assessed by affinity blotting using biotinylated trypsin to detect SPIs and by Western blotting using antibodies to α1-microglobulin, bikunin, TSG-6 and 2-B-6 (+) CS epitope generated by chondroitinase-ABC digestion. Results: 2-B-6 (+) positive 250, 220,120, 58 and 36 kDa SPIs were detected. The 58 kDa SPI contained α1-microglobulin, bikunin and chondroitin-4-sulfate stub epitope consistent with an identity of α1-microglobulin-bikunin (AMBP) precursor and was also isolated by concanavalin-A lectin affinity chromatography indicating it had N-glycosylation. Kunitz protease inhibitor (KPI) species of 36, 26, 12 and 6 kDa were autolytically generated by prolonged storage of the 120 and 58 kDa SPIs; chymotrypsin affinity chromatography generated the 6 kDa SPI. KPI domain 1 and 2 SPIs were separated by concanavalin lectin affinity chromatography, domain 1 displayed affinity for this lectin indicating it had N-glycosylation. KPI 1 and 2 displayed potent inhibitory activity against trypsin, chymotrypsin, kallikrein, leucocyte elastase and cathepsin G. Localisation of versican, lubricin and hyaluronan (HA) in the surface regions of articular cartilage represented probable binding sites for the ITI serine proteinase inhibitors (SPIs) which may preserve articulatory properties and joint function. Discussion/Conclusions: The Kunitz SPI proteins synthesised by articular chondrocytes are members of the ITI superfamily. By analogy with other tissues in which these proteins occur we deduce that the cartilage Kunitz SPIs may be multifunctional proteins. Binding of the cartilage Kunitz SPIs to HA may protect this polymer from depolymerisation by free radical damage and may also protect other components in the cartilage surface from proteolytic degradation preserving joint function.

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“…7,8 In addition, our previous study demonstrated that expressions of matrix metalloproteinases (MMPs) were significantly elevated in type 2 DM than those in diabetes-free OA patients and healthy controls. 9 Also, the phenomenon that high concentration of Glc affects chondrocytes and cartilage metabolism has also been observed in experimental studies. One study found that 25 nM Glc attenuated proteoglycan synthesis induced by IGF-1 in rabbit chondrocytes.…”

Section: Introductionmentioning

confidence: 88%

Long non-coding RNA PVT1, a molecular sponge of miR-26b, is involved in the progression of hyperglycemia-induced collagen degradation in human chondrocytes by targeting CTGF/TGF-β signal ways

Ding¹,

Li²,

Liu³

et al. 2019

Innate Immun

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The current study was conducted to investigate the role of long non-coding RNA PVT1 in hyperglycemia-triggered human osteoarthritis (OA) chondrocytes. Cartilage from knee OA patients with and without diabetes, as well as normal cartilage, was obtained. Isolated human chondrocytes were treated with 30 nM of Glc with or without pioglitazone. The expression levels of PVT1, miR-26b, and type II collagen were determined by RT-PCR. Type II collagen was detected by immunocytochemistry and chondrocytes were stained with Alcian blue. Moreover, the interaction among PVT1, miR-26b, and CTGF was examined using bioinformatics, FISH, RIP, RNA-pull down, and luciferase reporter assays. Over-expression of PVT1 and miR-26b were performed and expressions of CTGF, TGF-β1, SMAD3, MMP-13, and type II collagen proteins were examined. Significantly higher expression of PVT1 was observed in diabetic OA. High Glc induced the elevated expression of PVT1, CTGF, TGF-β1, IL-6, and MMP-13, as well as decreased expression of type II collagen and miR-26b. These alterations could be reversed by pioglitazone. PVT1 acted as a sponge for miR-26b to facilitate CTGF expression. Over-expression of PVT1 increased the expressions of CTGF, TGF-β1, SMAD3, and MMP-13 and decreased expression of type II collagen. Our findings confirmed that PVT1 is involved in the hyperglycemia-induced collagen degradation, via the miR-26b-CTGF-TGF-β1-axis.

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Expression and Significance of MMPs in Synovial Fluid, Serum and PBMC Culture Supernatant Stimulated by LPS in Osteoarthritis Patients With or Without Diabetes

Abstract: High levels of MMP-1, -7, -8, -9, -10, and -12 in the synovial fluid might be one of important reasons that diabetes patients are more frequently suffered from OA. Inflammation-induced malfunction of mononuclear cells would stimulate MMP-8 and -9 secretion to various extents.

Cited by 20 publications

References 39 publications

Matrix Metalloproteinases and Their Inhibitors and Proteoglycan 4 in Patients Undergoing Total Joint Arthroplasty

Matrix Metalloproteinases and Their Inhibitors and Proteoglycan 4 in Patients Undergoing Total Joint Arthroplasty

A Retrospective Analysis of the Cartilage Kunitz Protease Inhibitory Proteins Identifies These as Members of the Inter-α-Trypsin Inhibitor Superfamily with Potential Roles in the Protection of the Articulatory Surface

Long non-coding RNA PVT1, a molecular sponge of miR-26b, is involved in the progression of hyperglycemia-induced collagen degradation in human chondrocytes by targeting CTGF/TGF-β signal ways

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