A Histologic and Immunohistochemical Study of Calcium Pyrophosphate Dihydrate Crystal Deposition Disease

Masuda, Ikuko; Ishikawa, Kôichirô; Usuku, Gentaro

doi:10.1097/00003086-199102000-00034

Cited by 37 publications

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“…Crystal deposits of calcium pyrophosphate dihydrate (CPPD), cuboid microstructures (characterized as magnesium whitlockite) and hydroxyapatite (HA) have been observed in degenerated IVD specimens [15,[18][19][20]. In articular cartilage, regions with crystals showed altered amounts of collagen, calciumbinding proteins, decorin and large proteoglycan content, as well as abnormal pericellular matrix deposition [21,22]. Phagocytosis of crystals present in joints and pericellular tissues can trigger activation of the NOD-like receptor family pyrin domain containing 3 (NALP3) inflammasome.…”

Section: The Origin Of Inflammation In Intervertebral Discmentioning

confidence: 99%

Inflammation in intervertebral disc degeneration and regeneration

Molinos

Almeida

Caldeira

et al. 2015

J. R. Soc. Interface.

327

256

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Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players.

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Section: The Origin Of Inflammation In Intervertebral Discmentioning

confidence: 99%

Inflammation in intervertebral disc degeneration and regeneration

Molinos

Almeida

Caldeira

et al. 2015

J. R. Soc. Interface.

327

256

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“…CPPD crystals are rarely found in areas of normal articular cartilage matrix (Bjelle 1981), suggesting that alterations in matrix composition and/or ion composition are necessary for crystallization. Ishikawa et al demonstrated fragmented type II collagen fibers, loss of large proteoglycans, and increased levels of calcium-binding matricellular proteins in cartilage affected by CPPD crystal deposits (Ishikawa et al 1989;Masuda et al 1991). Matrix-modifying enzymes known as transglutaminases have also been implicated in CPPD crystal formation ).…”

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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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“…Our preliminary work (28) and that of Ishikawa et a1 (12) and Masuda et al (13) demonstrated that the smallest densities suggestive of CPPD crystals could be related to collagen fibers. In support of our limited earlier observations, we provide more extensive EM evidence of the close association of small CPPD with collagen fibers in synovium as well as in cartilage.…”

Section: Discussionmentioning

confidence: 51%

Calcium pyrophosphate dihydrate crystal deposition in synovium. relationship to collagen fibers and chondrometaplasia

Beutler

Rothfuss

Clayburne

et al. 1993

Arthritis & Rheumatism

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Objective. Reasons for apparent primary deposition of calcium pyrophosphate dihydrate (CPPD) crystals in some synovial membranes have not been systematically examined. We undertook the present study to investigate for and compare possible cellular and matrix factors related to the presence of these crystals in synovium and cartilage.Methods. Ten synovial membrane specimens and 6 cartilage specimens were obtained at the time of joint surgery from 10 patients with CPPD crystal deposition disease, for light microscopic (LM) and electron microscopic (EM) studies.Results. In all synovial and cartilage specimens, we found many of the small CPPD crystals aligned on or in parallel to collagen fibers, as seen by EM. In 9 of the Submitted for publication September 9, 1992; accepted in revised form December 1. 1992. 10 crystal-containing synovia, we found foci of chondrometaplasia adjacent to CPPD, by LM. In 7 of the synovia, including the one without LM evidence of chondrometaplasia, we observed the presence of chondrocytelike cells by EM. We did not note any predictable relationship between the crystals and matrix vesicles, either in synovium or in cartilage.Conclusion. Our EM findings provide evidence of the relationship of small CPPD-like crystals, presumably early forms, to collagen fibers both in synovium and in cartilage. By LM and EM, we also demonstrate evidence of a close association between chondrometaplasia and CPPD deposits in synovium. We suggest that chondrometaplasia might be responsible for synovial CPPD formation in predisposed patients. Both the collagen fibers and chondrocyte-like cells seem to be involved in the primary formation of CPPD deposits in the synovium as well as in the cartilage.In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, crystals appear to deposit virtually only in articular and periarticular connective tissues, mainly fibrocartilage, hyaline cartilage, and synovium, and, less often, in tendons, ligaments, and bursae (1-3). The proposed mechanisms involved in CPPD deposition in cartilage include increased production or impaired removal of calcium and inorganic pyrophosphate (PPJ (1,2,4-6), decreased magnesium concentrations (7,8), and various cellular and matrix factors, which can promote, nucleate, or inhibit crystal deposition (1,2,9).Local tissue factors probably play an important role in CPPD deposition disease and possibly determine the preferential articular localization of crystal deposits. McCarty et a1 described CPPD deposits

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A Histologic and Immunohistochemical Study of Calcium Pyrophosphate Dihydrate Crystal Deposition Disease

Cited by 37 publications

References 0 publications

Inflammation in intervertebral disc degeneration and regeneration

Inflammation in intervertebral disc degeneration and regeneration

Osteopontin promotes pathologic mineralization in articular cartilage

Calcium pyrophosphate dihydrate crystal deposition in synovium. relationship to collagen fibers and chondrometaplasia

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