Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies

Nalbant, Selim; Martinez, José A.; Kitumnuaypong, Tasanee; Clayburne, G.; Sieck, M.; Schumacher, H. Ralph

doi:10.1053/joca.2002.0861

Cited by 185 publications

(106 citation statements)

References 23 publications

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“…Fuerst and colleagues' report reinforces the hypothesis of a pathologic role of BCPs in OA, as previously suggested by numerous clinical and laboratory studies such as that reported by Nalbant and colleagues, which showed that the presence of BCPs in OA synovial fluid (SF) predicted increased cartilage destruction (2). In vivo, in OA animal models such as guinea pig and STR/ort mouse models, meniscus calcifications preceded cartilage breakdown (3,4).…”

Section: To the Editorsupporting

confidence: 72%

Osteoarthritis, a basic calcium phosphate crystal–associated arthropathy? Comment on the article by Fuerst et al

Nguyen¹,

Ea²,

Bazin³

et al. 2010

Arthritis & Rheumatism

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A new method of introducing dithioester groups into the polymer chain of poly(cyclohexene oxide) is reported. It includes the use of diaryliodonium salt and an aromatic dithioacid as a redox couple to initiate the cationic polymerization of cyclohexene oxide. It was found that the dithioacid by itself cannot start the polymerization of cationic polymerizable monomers; however, in combination with a diaryliodonium salt, an exothermic reaction was produced, yielding a thiocarbonylthio‐functionalized polyether. Thermal profiles of the redox polymerizations were determined by means of optical pyrometry. A preliminary study showed that when the poly(cyclohexene oxide) functionalized with dithioester groups was introduced into the radical polymerization of styrene, the polystyryl growing radicals reacted with the dithioester‐functionalized polyether to form a block polymer. The amount of polyether actually incorporated into the block copolymer was calculated to be 70% of the initial amount of poly(cyclohexene oxide)/dithiobenzoic acid charged into the reactor. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

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Section: To the Editorsupporting

confidence: 72%

Osteoarthritis, a basic calcium phosphate crystal–associated arthropathy? Comment on the article by Fuerst et al

Nguyen¹,

Ea²,

Bazin³

et al. 2010

Arthritis & Rheumatism

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“…In vitro, calcium-containing crystals induce the release of catabolic cytokines and proteases from synovial cells and chondrocytes (Cheung 2001). Clinically, their presence predicts increased severity of joint damage and more rapid progression of joint destruction (Ledingham et al 1993;Nalbant et al 2003). …”

Section: Introductionmentioning

confidence: 99%

Osteopontin promotes pathologic mineralization in articular cartilage

et al. 2007

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Calcium pyrophosphate dihydrate (CPPD) crystals are commonly found in osteoarthritic joint tissues, where they predict severe disease. Unlike other types of calcium phosphate crystals, CPPD crystals form almost exclusively in the pericellular matrix of damaged articular cartilage, suggesting a key role for the extracellular matrix milieu in their development. Osteopontin is a matricellular protein found in increased quantities in the pericellular matrix of osteoarthritic cartilage. Osteopontin modulates the formation of calcium-containing crystals in many settings. We show here that osteopontin stimulates ATP-induced CPPD crystal formation by chondrocytes in vitro. This effect is augmented by osteopontin's incorporation into extracellular matrix by transglutaminase enzymes, is only modestly affected by its phosphorylation state, and is inhibited by integrin blockers. Surprisingly, osteopontin stimulates transglutaminase activity in cultured chondrocytes in a dose responsive manner. As elevated levels of transglutaminase activity promote extracellular matrix changes that permit CPPD crystal formation, this is one possible mechanism of action. We demonstrate the presence of osteopontin in the pericellular matrix of chondrocytes adjacent to CPPD deposits and near active transglutaminases. Thus, osteopontin may play an important role in facilitating CPPD crystal formation in articular cartilage. KeywordsOsteopontin; Calcium pyrophosphate dihydrate; Transglutaminase; Osteoarthritis Pathologic matrix mineralization is a common occurrence in joints affected by late stage osteoarthritis. Of synovial fluids sampled at the time of knee replacement, for example, 60% contain pathologic calcium-containing crystals (Derfus et al. 2002). Both calcium pyrophosphate dihydrate (CPPD) and hydroxyapatite-like basic calcium phosphate (BCP) crystals occur in osteoarthritic joints. Although the role that calcium-containing crystals play in osteoarthritis is not fully understood, there is ample evidence to suggest that these crystals are active participants in joint damage. In vitro, calcium-containing crystals induce the release of catabolic cytokines and proteases from synovial cells and chondrocytes (Cheung 2001). Clinically, their presence predicts increased severity of joint damage and more rapid progression of joint destruction (Ledingham et al. 1993;Nalbant et al. 2003).Corresponding Author: Ann K. Rosenthal, MD Rheumatology Section/ cc-111W Zablocki VA Medical Center 5000 W. National Ave. Milwaukee, WI 53295-1000 TEL: 414-384-2000ann.rosenthal@med.va.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply ...

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“…BCP crystal deposition in knee articular cartilage is correlated with cartilage destruction and more severe lesions (1). Their presence in synovial fluid predicts radiological OA progression (3). Extra-articular depositions of BCP crystals are mostly asymptomatic but can give rise to acute inflammatory attacks.…”

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confidence: 99%

Basic Calcium Phosphate Crystals Induce Monocyte/Macrophage IL-1β Secretion through the NLRP3 Inflammasome In Vitro

Pazár

Narayan

et al. 2011

The Journal of Immunology

225

143

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Basic calcium phosphate (BCP) crystals are associated with severe osteoarthritis and acute periarticular inflammation. Three main forms of BCP crystals have been identified from pathological tissues: octacalcium phosphate, carbonate-substituted apatite, and hydroxyapatite. We investigated the proinflammatory effects of these BCP crystals in vitro with special regard to the involvement of the NLRP3–inflammasome in THP-1 cells, primary human monocytes and macrophages, and mouse bone marrow-derived macrophages (BMDM). THP-1 cells stimulated with BCP crystals produced IL-1β in a dose-dependent manner. Similarly, primary human cells and BMDM from wild-type mice also produced high concentrations of IL-1β after crystal stimulation. THP-1 cells transfected with short hairpin RNA against the components of the NLRP3 inflammasome and mouse BMDM from mice deficient for NLRP3, apoptosis-associated speck-like protein, or caspase-1 did not produce IL-1β after BCP crystal stimulation. BCP crystals induced macrophage apoptosis/necrosis as demonstrated by MTT and flow cytometric analysis. Collectively, these results demonstrate that BCP crystals induce IL-1β secretion through activating the NLRP3 inflammasome. Furthermore, we speculate that IL-1 blockade could be a novel strategy to inhibit BCP-induced inflammation in human disease.

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Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies

Cited by 185 publications

References 23 publications

Osteoarthritis, a basic calcium phosphate crystal–associated arthropathy? Comment on the article by Fuerst et al

Osteoarthritis, a basic calcium phosphate crystal–associated arthropathy? Comment on the article by Fuerst et al

Osteopontin promotes pathologic mineralization in articular cartilage

Basic Calcium Phosphate Crystals Induce Monocyte/Macrophage IL-1β Secretion through the NLRP3 Inflammasome In Vitro

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