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PubMed2003

He-Ne laser on microcrystalline arthropathies.

OBJECTIVE: The objective of this work is to assess the anti-inflammatory capacity of He-Ne laser therapy as determined by the plasmatic levels of inflammatory markers, fibrinogen, and TNFalpha and by histopathological study in rats with arthropathy induced by calcium pyrophosphate crystals. BACKGROUND DATA: Microcrystalline arthropathies are a group of diseases characterized by the deposit of different crystals in joints. MATERIALS AND METHODS: Two milligrams of dicalcium pyrophosphate crystals (DCPP) were injected in both joints of the lower limbs of rats during 2 days. A group was treated with laser of He-Ne (6 mW) on the injected joints during 3 consecutive days. After 96 h of the first injection, animals were sacrificed to determine TNFalpha using the ELISA method and fibrinogen was assessed using spectrophotometry. Sections from the lower limbs were used for histopathology. RESULTS: A statistically significant increase (p < 0.001) in plasma fibrinogen levels and TNFalpha was noted between the control group and the laser-treated group. The histological transversal section of a posterior limb joint of a rat injected with DCPP showed fibroadipose tissue with diffuse chronic infiltrate. The histopathology of the group of rats injected with DCPP and subsequently treated with He-Ne laser showed no inflammatory response. CONCLUSION: He-Ne laser treatment in the microcrystalline arthropathy induced in rats by DCPP injection might have an antiinflammatory effect, evaluated by fibrinogen plasma levels and TNF-alpha (inflammatory markers) and by the histopathology regressive process.

Analysis of Variance↗
PubMed1991

Crystal-induced inflammation: studies of the mechanism of crystal-membrane interactions.

Studies of the interactions of monosodium urate monohydrate (MSUM) crystals and calcium pyrophosphate dihydrate triclinic (CPPD) crystals with biomembranes have been reviewed. Crystal-membrane binding and crystal-induced membranolysis have been studied using human erythrocytes as a model membrane system. The extent of MSUM-membrane binding was determined by incorporating a hydrophobic, fluorescent probe into the membranes, centrifugation to separate free membranes from membranes with bound crystals and quantitation of free membranes by measuring the total fluorescence intensity. The ability of MSUM and CPPD to hemolyse red cells was used as a measure of the membranolytic potential of the crystals. Fluorescence polarization studies showed that MSUM-membrane binding resulted in fluidization of the membrane. Cross-linking of the membrane proteins of the erythrocyte or the presence of divalent cations in the incubation medium inhibited MSUM induced hemolysis. These findings were explained by hypothesizing a "pore" model mechanism for MSUM induced membranolysis as follows. Binding of crystals to membranes induces the redistribution of transmembrane proteins into clusters or aggregates leading to "pore" formation. The "pores" permit the leakage of low molecular weight soluble compounds and ions acoss the membrane which is followed by osmotic rupture of the membrane.

Arthritis↗
PubMed1993

Crystal-induced neutrophil activation. II. Evidence for the activation of a phosphatidylcholine-specific phospholipase D.

OBJECTIVE: To investigate the involvement of phospholipase D in the signaling pathways activated by 2 pathologically relevant inflammatory microcrystals, monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD). METHODS: Human peripheral blood neutrophils were used throughout. Phospholipase D activity was monitored by measuring 3 separate indices: 1) the mass of phosphatidic acid, 2) the levels of alkyl-phosphatidic acid, and 3) the levels of formation, in the presence of ethanol, of phosphatidylethanol. The latter 2 parameters were measured in cells labeled with 1-0-3H-alkyl-2-acetyl-sn-glycero-3-phosphocholine. The cells were stimulated with microcrystals of triclinic morphology. RESULTS: Both MSU and CPPD crystals induced a time- and concentration-dependent accumulation of phosphatidic acid mass and elevation in levels of alkyl-phosphatidic acid and phosphatidylethanol in prelabeled cells. The activation of phospholipase D by the microcrystals was partially sensitive to colchicine and largely resistant to pertussis toxin. Inhibition of phosphatidic acid formation by wortmannin or ethanol reduced the microcrystal-stimulated production of superoxide anions. CONCLUSION: These results indicate that microcrystals stimulate phospholipase D in human neutrophils and that at least some of the functional consequences of neutrophil-microcrystal interactions may be dependent on this biochemical pathway.

Androstadienes↗
PubMed1996

Crystal-induced arthritis: an overview.

The most common crystal-related arthropathies-gout, calcium pyrophosphate dihydrate disease or "pseudogout," and calcific periarthritis/tendinitis-may be appropriately diagnosed and managed by the primary care physician. Definitive diagnosis via synovial tap is recommended, as the clinical picture may not identify some cases. The acute pain and swelling of attacks, regardless of etiology, generally respond to treatment with nonsteroidal anti-inflammatory drugs and local or occasionally systemic corticosteroids. Once a causative crystal has been identified and a diagnosis established, a plan for long-term management and prevention of recurrences may be devised. Thus, uric-acid-lowering therapy may be indicated in a patient who has experienced recurrent attacks of gout, whereas control of serum phosphate levels might be effective in some individuals with hyperphosphatemia and hydroxyapatite-associated periarthritis or arthritis. Crystal deposits in joints can be destructive as well as painful. Treatment, therefore, has two objectives: To relieve the pain of the acute attack, thus restoring normal function, and to prevent the accumulation of crystals that can lead to degenerative disease. Identification and subsequent treatment of preventable or correctable underlying disorders may be one of the most gratifying aspects of managing crystal-induced arthropathies.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1984

Modification of thymo-dependent and thymo-independent antibody responses during non-specific acute inflammation.

An acute non-immunological inflammatory reaction, induced in mice by injecting intrapleurally a non-bacterial, non-antigenic and endotoxin-free irritant (40,000 molecular weight dextran or monoclinic dihydrated calcium pyrophosphate microcrystals), provoked an increase of antibody responses to thymus-dependent SRBC or thymus-independent TNP-LPS or DNP-Ficoll when the phlogistic stimulus was applied before immunisation. The increase in the number of IgM plaque-forming cells per spleen was obtained for different time intervals between the induction of the inflammatory stimulus and the antigen administration according to the type of irritant and the antigen used. However, no stimulation could be observed when this time interval was greater than three days. No stimulation of the antibody response to SRBC was observed when the irritant was applied one to three days after the antigen. The (stimulatory) effect could not be entirely related to a polyclonal activation as an augmentation in the production of antibody against non-cross-reactive antigen could only be seen four days after the onset of the inflammatory process, when the specific antibody response was not maximal. These observations indicate that an acute non-immunological inflammatory reaction lasting for 48 h can affect the immune reactivity of the host, even after the inflammatory process has disappeared.

Acute Disease↗
PubMed2005

Analysis for crystals in synovial fluid: training of the analysts results in high consistency.

BACKGROUND: Identification of monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPPD) crystals in synovial fluid samples is diagnostic of gout and CPPD crystal related arthropathy. Various studies have shown poor consistency in results of crystal analysis. OBJECTIVE: To determine whether training of the analysts increases the consistency. METHODS: An expert rheumatologist gave a course on crystal detection and identification. The four trained observers then blindly and independently examined synovial fluid samples previously classified by the expert which had been obtained from patients with both crystal arthropathies and other non-crystal related inflammatory joint conditions. RESULTS: 194 observations were made on 64 synovial fluid samples: 96 without crystals (49.4%), 55 with CPPD crystal (28.4%), and 43 with MSU crystals (22.2%). For crystal detection (presence or absence of crystals), sensitivity was 95.9% and specificity 86.5%. For identification of MSU crystals, sensitivity was 95.3% and specificity 97.2%. For identification of CPPD crystals, sensitivity was 92.7% and specificity 92.1%. The kappa index of agreement with the reference standard between the observers was 0.84 for any crystal detection, 0.93 for MSU crystal sample identification, and 0.79 for CPPD crystal sample identification. CONCLUSIONS: For trained observers, the detection and identification of crystals in synovial fluid is a consistent procedure.

Arthritis↗
PubMed1995

Even low-grade synovitis significantly accelerates the clearance of protein from the canine knee. Implications for measurement of synovial fluid "markers" of osteoarthritis.

OBJECTIVE: In recent studies, the synovial fluid concentration of molecules derived from the extracellular matrix of articular cartilage has been used to deduce the magnitude of cartilage destruction or repair in osteoarthritic (OA) joints. Because low-grade synovitis is often present in such joints, we assessed the effect of synovial inflammation on the clearance of a prototypical protein, albumin, from synovial fluid. METHODS: 131I-labeled albumin (RISA) was injected into 1 (control) knee of each of 14 dogs. The concentration of RISA in synovial fluid aspirated 7 hours after the injection and serial measurements of surface radioactivity were used to calculate the volume of distribution (Vd) and clearance of RISA. One week later, synovitis was induced in the contralateral knee by intraarticular injection of various quantities of calcium pyrophosphate dihydrate (CPPD) crystals, after which RISA was injected into that joint and these measurements were repeated. RESULTS: Intraarticular injection of 500 micrograms of CPPD crystals produced intense synovitis, with a mean synovial fluid white blood cell (WBC) count of 43,200 cells/mm3, and values for RISA Vd and RISA clearance (36.5 ml and 33.7 microliters/minute) were much higher than those for saline-injected control knees (2.7 ml and 1.5 microliters/minute, respectively). Injection of 0.5 microgram of CPPD also produced marked synovitis and values for Vd and RISA clearance that were 2-3-fold greater than those in the contralateral knee. The low-grade synovitis produced by only 0.05 microgram of CPPD, which resulted in synovial fluid WBC counts as low as 1,000-2,000 cells/mm3, was accompanied by increases in the clearance and Vd of RISA to levels approximately 40% and approximately 80% higher, respectively, than those for the contralateral knee. CONCLUSION: Even mild synovitis, as seen in OA, may significantly increase the clearance of a protein from the joint. Synovitis is a significant variable which must be considered in studies of putative chondroprotective drugs if conclusions about the effects of drugs on cartilage metabolism are to be drawn from changes in the synovial fluid concentration of a "marker" protein.

Albumins↗
PubMed2004

Transglutaminase contributes to CPPD crystal formation in osteoarthritis.

Calcium pyrophosphate dihydrate (CPPD) crystals are common components of osteoarthritic joints and correlate with a poor prognosis. Transglutaminase (Tgase) enzymes have been implicated in pathologic mineralization in cartilage; yet, definitive studies linking Tgase activity to CPPD crystal formation in osteoarthritic articular cartilage are lacking. We measured in-vivo Tgase activity in osteoarthritic and normal human cartilage, and explored the effect of Tgase inhibitors on CPPD crystal formation by normal chondrocytes. Osteoarthritic articular cartilage from was obtained from specimens discarded at the time of knee replacement surgery. Normal adult cartilage samples from a tissue bank were used as controls. Tgase-specific isopeptide (epsilon-(gamma-glutamyl) lysine) bonds were measured in cartilage extracts by HPLC. Tgase-specific crosslinks were localized in osteoarthritic cartilage by immunohistochemistry. The effect of Tgase inhibition was determined in an in-vitro model of CPPD crystal formation. Tgase-specific crosslink levels were 1.55 +/- 0.3 picomoles/ng protein in normal human adult articular cartilage and 4.74 +/- 0.7 picomoles/ng protein in osteoarthritic human cartilage (p less than 0.001). Immunostaining confirmed the presence of Tgase crosslinks in the pericellular matrix of chondrocytes at potential sites of CPPD crystal formation. Tgase inhibitors suppressed CPPD crystal formation by porcine chondrocytes. These findings support a role for Tgase in CPPD crystal formation in aging or degenerated cartilage.

Animals↗
PubMed2002

Inflammatory microcrystals alter the functional phenotype of human osteoblast-like cells in vitro: synergism with IL-1 to overexpress cyclooxygenase-2.

Chronic crystal-associated arthropathies such as gout and pseudogout can lead to local bone destruction. Because osteoblasts, which orchestrate bone remodeling via soluble factors and cell-to-cell interactions, have been described in contact with microcrystals, particularly in uratic foci of gout, we hypothesized that microcrystals of monosodium urate monohydrate (MSUM) and of calcium pyrophosphate dihydrate (CPPD) could alter osteoblastic functions. MSUM and CPPD adhered to human osteoblastic cells (hOB) in vitro and were partly phagocytized as shown by scanning electron microscopy. MSUM and CPPD dose-dependently stimulated the production of PGE(2) in hOB as assessed by enzyme immunoassay, a response that was synergistically enhanced in the presence of IL-1. The mechanism of this synergism was, at least in part, at the level of the expression of cyclooxygenase-2 as evaluated by immunoblot analysis. MSUM and CPPD also stimulated the expression of IL-6 and IL-8 and reduced the 1,25-dihydroxyvitamin D(3)-induced activity of alkaline phosphatase and osteocalcin in hOB (with no synergism with IL-1). MSUM- or CPPD-stimulated expression of IL-6 in hOB pretreated with the selective cyclooxygenase-2 inhibitor NS-398 was increased, unlike that induced by IL-1 alone which was partially reduced. MSUM-, CPPD- or IL-1-induced expression of IL-8 was unchanged by pretreating hOB with NS-398. These results suggest that inflammatory microcrystals alter the normal phenotype of hOB, redirecting them toward reduced bone formation and amplified osteoblast-mediated bone resorption, abnormalities that could play a role in the bone destruction associated with chronic crystal-induced arthritis.

Adjuvants, Immunologic↗
PubMed1993

Crystal-induced neutrophil activation. IV. Specific inhibition of tyrosine phosphorylation by colchicine.

We recently demonstrated that pathologically relevant inflammatory microcrystals, namely triclinic monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals, potently stimulate a characteristic protein tyrosine phosphorylation pattern in human neutrophils that differed from that observed in response to other soluble or particulate agonists. In this study, the effects of colchicine on protein tyrosine phosphorylation induced by MSU and CPPD crystals in human blood neutrophils were investigated. Immunoblot analysis with antiphosphotyrosine antibodies demonstrated that colchicine dose-dependently inhibited the tyrosine phosphorylation of all the proteins phosphorylated in response to MSU and CPPD crystals. Other microtubule-disruptive agents such as vinblastine, nocodazole, and colcemid also inhibited crystal-induced protein tyrosine phosphorylation while lumicolchicine and trimethylcolchicinic acid were without effect. Indomethacin and phenylbutazone were similarly without effect on microcrystal-induced tyrosine phosphorylation. Colchicine, as well as the other active alkaloids, failed to inhibit the protein tyrosine phosphorylation elicited by FMLP, C5a, leukotriene B4, and unopsonized zymosan. Overall, these results demonstrate that colchicine specifically and significantly inhibits the protein tyrosine phosphorylation induced by MSU and CPPD crystals and suggest that its effects are associated, at least in part, with its interaction with microtubules. Furthermore, the use of microtubule-disrupting drugs demonstrate that the mechanisms implicated in the induction of protein tyrosine phosphorylation by microcrystals differed from those involved in response to other soluble or particulate agonists.

Blood Proteins↗
PubMed1984

In vivo interaction of nonsteroidal anti-inflammatory drugs on the locomotion of neutrophils elicited by acute non-specific inflammations in the rat--effect of indomethacin, ibuprofen and flurbiprofen.

The in vivo effects of Flurbiprofen, Ibuprofen and Indomethacin (1.5, 6 and 3 mg/kg respectively) were studied on two acute non-specific pleurisies induced by calcium pyrophosphate crystals (CaPP) or decomplemented isologous rat serum (DIRS) in the rat. Drug effects on the exudation phase (pleural exudate volume), leukocyte emigration (number of leukocytes in the fluid) and on random and directed locomotion of elicited neutrophils (PMN) under agarose were investigated. In the CaPP model, Indomethacin, Flurbiprofen and Ibuprofen reduced the pleural exudate volume by approximately 48, 57 and 22% respectively while leukocyte emigration was inhibited 50, 45 and 50% respectively. In the DIRS model Indomethacin and Flurbiprofen reduced the exudate volume by 54 and 52% and leukocyte emigration by 51 and 31% respectively. Ibuprofen administration produced a decrease in exudate volume of only 27%. The three drugs did not alter in vitro locomotion of DIRS-elicited PMN. On the other hand, Flurbiprofen reduced both random and directed locomotion of CaPP-elicited PMN stimulated with peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), isologous rat serum (IRS) or cell-free exudates. Ibuprofen induced a slight increase in random migration of CaPP-elicited PMN while Indomethacin was without effect. None of the three drugs altered the chemotactic activity of inflammatory exudate. These data suggest that therapeutic doses of anti-inflammatory drugs interfere with PMN at inflammatory sites and induce modifications in their movement per se which persist after cell washing.

Animals↗
PubMed1995

Mechanical properties and histological evaluation of sintered beta-Ca2P2O7 with Na4P2O7.10H2O addition.

The ultimate goal of implantation of biomaterials in the skeleton is to reach full integration of the non-living implant with the living bone. The biomaterial can be used much as a bone graft, resorbing or dissolving as bone growth occurs, and the end result is a new remoulded bone. Calcium pyrophosphate, Ca2P2O7, is one of the intermediate products of bone mineralization. beta-Dicalcium pyrophosphate (beta-DCP) doped with certain amounts of Na4P2O7.10H2O was prepared as the developed material. Na4P2O7.10H2O was used as a liquid-phase additive to improve the sintering process and promote physiological bioresorbability. Compressive strength and four-point bending strength were measured by the Bionix test system 858. The mechanical strength of the sintered beta-DCP increased with the addition of Na4P2O7.10H2O up to 5 wt%, but thereafter decreased. The microstructure and crystal structure were analysed by the techniques of SEM, EPMA, TEM and XRD. The relationship between the mechanical strength of the sintered bioceramics and the Na4P2O7.10H2O dopant was examined in terms of the presence of NaCa(PO3)3, grain growth and abnormal grain coalescence while the dopant increased. Preliminary in vivo evaluation was studied by rabbit femur condyle implantation. There was no inflammation or any toxic sign during the experimental period. The histological section of intraosseous implantation revealed that the new bone deposited directly on the surface of the material in the fourth week after operation. The implant gradually decreased in volume and was replaced by the surrounding regenerated bone in the rabbit condyle in vivo environment. The results led us to conclude that the developed material has great potential as a biodegradable bone substitute.

Animals↗
PubMed1999

Thyroid hormones induce features of the hypertrophic phenotype and stimulate correlates of CPPD crystal formation in articular chondrocytes.

OBJECTIVE: Articular cartilage affected by calcium pyrophosphate dihydrate (CPPD) crystal deposition contains abnormal chondrocytes with morphologic similarities to the terminally differentiated hypertrophic chondrocytes that mineralize in growth plate cartilage. These chondrocytes also elaborate high levels of extracellular inorganic pyrophosphate (PPi), an essential component of the CPPD crystal. Several factors that stimulate articular chondrocyte PPi elaboration also induce terminal differentiation in growth plate chondrocytes. We hypothesized that factors such as thyroid hormones (T3 and T4) that are potent stimulants of growth plate chondrocyte hypertrophy might also stimulate articular chondrocyte hypertrophic differentiation. We also hypothesized that like transforming growth factor-beta (TGF-beta), ascorbate, and retinoic acid, thyroid hormones would increase chondrocyte PPi elaboration. METHODS: We determined the effects of T3, T4, and TGF-beta on markers of the hypertrophic phenotype such as alkaline phosphatase (ALPase) activity and type X collagen production; and the effects of T3 and T4 on processes implicated in CPPD crystal formation including PPi elaboration and nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity in adult porcine articular chondrocytes in culture. RESULTS: ALPase activity increased 3-fold with T3 and T4 and 1.3-fold with TGF-beta. Type X collagen levels also increased with thyroid hormone treatment. [125I]T3 binding studies proved the existence of saturable T3 receptors on chondrocytes. Media [PPi] and cellular NTPPPH activity significantly increased in cultures treated with 1-10 nM T3 or 100-500 nM T4. CONCLUSION: Increased PPi elaboration is an additional and previously unrecognized feature of hypertrophic differentiation in articular chondrocytes. These terminally differentiated chondrocytes may play a pathogenic role in CPPD crystal deposition disease.

Alkaline Phosphatase↗
PubMed1995

Inflammatory microcrystals differentially regulate the secretion of macrophage inflammatory protein 1 and interleukin 8 by human neutrophils: a possible mechanism of neutrophil recruitment to sites of inflammation in synovitis.

Human neutrophils at inflammatory sites may be an important source of the chemotactic cytokines macrophage inflammatory protein 1 alpha (M1P-1 alpha; a C-C chemokine) and interleukin 8 (IL-8; a C-X-C chemokine). In this study, we show that the inflammatory microcrystals monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD), the major mediators of gout and pseudogout, differentially regulate the production of these two chemokines by human neutrophils. Both MSU and CPPD increased the secretion of IL-8 by neutrophils in a dose- and time-dependent manner, but had no effect on that of MIP-1 alpha. Since inflammatory cytokines are likely to be present in the synovium during crystal-induced inflammation, we examined the interaction between TNF-alpha and GM-CSF and the crystals. Both TNF-alpha and GM-CSF stimulated IL-8 production; however, only TNF-alpha exerted a significant effect on MIP-1 alpha secretion in neutrophils. IL-8 production induced by TNF-alpha and GM-CSF was synergistically enhanced in the presence of MSU or CPPD, whereas MIP-1 alpha secretion induced by TNF was completely inhibited in the presence of either MSU or CPPD. Interestingly, no interaction between the crystals and the inflammatory cytokines was observed with respect to synthesis of the C-X-C chemokine MGSA in neutrophils. These results suggest that the combination of TNF-alpha and GM-CSF with MSU or CPPD will lead to the production of IL-8 by neutrophils and abolish the release of MIP-1 alpha, an event that will theoretically lead to recruitment of neutrophils but not mononuclear cells. These results are in accordance with the pathological state of gout and pseudogout, where the predominant inflammatory cell is the neutrophil.

Calcium Pyrophosphate↗
PubMed2005

Intracellular and extracellular CPPD crystals are a regular feature in synovial fluid from uninflamed joints of patients with CPPD related arthropathy.

OBJECTIVES: To determine whether calcium pyrophosphate dihydrate (CPPD) crystals can be found in the synovial fluid of non-inflamed joints in patients with CPPD related arthropathy; if so, to determine whether they interact with cells and produce subclinical inflammation in this setting. METHODS: 74 synovial fluid samples were obtained from non-inflamed knees of 74 patients with CPPD related arthropathy. Identification of CPPD crystals and synovial fluid cell counts were done manually in undiluted samples using a haematocytometric chamber. A supravital stain (Testsimplets, Boehringer Mannheim) was used to carry out differential counts and to assess the presence of intracellular crystals. RESULTS: All 74 samples contained CPPD crystals. The mean cell count was 301.4 cells/microl (95% confidence interval (CI), 216.6 to 386.4; range 22 to 2302.5). Mononuclear cells accounted for 83.2% (95% CI, 80.4% to 86.1%; range 43% to 99%), the rest being polymorphonuclear (PMN) cells (16.8% (95% CI, 13.9% to 19.6%; range 1% to 57%)). All the samples contained intracellular CPPD crystals, which were found in 24.0% of all the cells (95% CI, 20.1% to 27.9%; range 1% to 78%). Most of the intracellular crystals were inside mononuclear cells (22.2% of all the cells (95% CI, CI 18.5% to 25.9%)), although some PMN also contained them (1.8% of all the cells (95% CI, 1.1% to 2.4%)). CONCLUSIONS: CPPD crystals are normally found in synovial fluid of non-inflamed joints of patients with CPPD related arthropathy, and they interact with cells. The raised cell counts and percentage of PMN suggest mild subclinical inflammation in these joints.

Adult↗
PubMed1994

[A role for lipoproteins in the recovery from CPPD crystal-induced arthritis].

Calcium pyrophosphate dihydrate (CPPD) crystal-induced inflammation subsides spontaneously, and there have been few reports on its mechanism. It has recently been proposed that lipoproteins in the inflammatory synovial fluid played a role in the recovery from crystal-induced arthritis. This study investigated the inhibitory effect of lipoprotein on the inflammation-inducing activity of CPPD crystals in vitro and in vivo. Lipoproteins (very low density lipoprotein--VLDL, and low density lipoprotein-LDL) were isolated from human serum (in vitro) and rat serum (in vivo) by the sequential ultracentrifugal technique. In the in vitro studies, saline with lipoproteins was mixed with CPPD crystals, and co-incubated with isolated polymorphonuclear leukocytes (PMN). The production of superoxide anion (O-(2)) was measured as an index of inflammatory activity. In the in vivo studies, suspensions of CPPD crystals and rat lipoprotein solutions, were injected into the rat air pouch. The total number of white blood cells (WBC), crystal-containing WBCs, and concentrations of beta-glucronidase and prostaglandin (PG) E2, were measured. In the in vitro studies, O-(2) production by PMNs was more significantly suppressed after treating the CPPD crystals with VLDL or LDL than when the crystals were not treated with VLDL or LDL. In the in vivo studies, treatment of the CPPD crystals with lipoproteins significantly decreased the number of WBC and crystal-containing WBC, as well as the concentration of beta-glucronidase, and tended to depress the concentration of PGE2. These findings suggested that lipoproteins, especially LDL in inflammatory synovial fluid played an important role in the recovery from CPPD crystal-induced arthritis.

Animals↗
PubMed1994

Crystal-induced neutrophil activation. V. Differential production of biologically active IL-1 and IL-1 receptor antagonist.

Neutrophils produce IL-1 when stimulated by monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals. Neutrophils also generate the IL-1R antagonist (IL-1Ra), especially when incubated with granulocyte-macrophage CSF (GM-CSF) or TNF-alpha. We studied the simultaneous expression of IL-1 and IL-1Ra by GM-CSF- or TNF-alpha-treated neutrophils activated by MSU or CPPD. Neutrophils incubated with GM-CSF or TNF-alpha produced approximately 300 or 200 times more IL-1Ra than IL-1, respectively. Suboptimal concentrations of MSU or CPPD induced low amounts of IL-1 without affecting IL-1Ra. Interaction of GM-CSF- and TNF-alpha-treated neutrophils with MSU or CPPD up-regulated IL-1 while simultaneously down-regulating IL-1Ra. As a result, the bioactivity of IL-1 secreted was enhanced. Synergistic increases of IL-1 (but not IL-1Ra) mRNA levels were noted in GM-CSF- or TNF-alpha-treated neutrophils exposed to CPPD. Treatment of neutrophils with colchicine before incubation with GM-CSF or TNF alpha, inhibited crystal-induced IL-1 by 50 to 55%, but failed to significantly affect IL-1Ra. The IL-1Ra to IL-1 ratio was significantly increased by 185 to 220%. These results demonstrate that IL-1 and IL-1Ra production by human neutrophils are differentially regulated, that the combined presence of GM-CSF or TNF-alpha and microcrystals favor the production of biologically active IL-1 over that of IL-1Ra, and that colchicine selectively inhibits IL-1 without affecting IL-1Ra production.

Calcium Pyrophosphate↗
PubMed2005

Biomechanical and histomorphometric study on the bone-screw interface of bioactive ceramic-coated titanium screws.

The purpose of this study was to compare the osseointegration of 4 different kinds of bioactive ceramic-coated screws with uncoated screws by biomechanical and histomorphometric analysis. Calcium pyrophosphate (CPP), apatite-wollastonite 1:3 glass ceramic (W3G), apatite-wollastonite 1:1 glass ceramic (WAG) and bioactive CaO-SiO2-B2O3 glass ceramic (CSG) coatings were prepared and coated by the dipping method. Coated and uncoated titanium screws were inserted into the tibia of 18 adult mongrel male dogs for 2, 4, and 8 weeks. The insertion torques, radiographs, undecalcified histology, histomorphometric analysis, and extraction torques were evaluated. No difference of insertion torque was found among the five screw types. At 2 and 4 weeks after implantation, the extraction torque of ceramic-coated screws was significantly higher than that of uncoated screws (p < or = 0.0001). At 8 weeks, the extraction torques of CPP-, W3G-, and WAG-coated screws were significantly higher than those of CSG-coated and uncoated screws (p<0.0001). At 2, 4, and 8 weeks, the extraction torques of 4 different ceramic-coated screws were significantly higher than the corresponding insertion torque. Strong fixation was observed even at 2 weeks in the CPP-, W3G- and WAG-coated screws. The bone-screw contacts of the 4 different coated screws at 2 and 4 weeks were statistically higher than that of the uncoated screws, and the bone-screw contacts of the CPP-, W3G- and WAG-coated screws at 8 weeks were also statistically higher than that of the uncoated screws. The fixation strength was increased by the presence of osteoconductive coating materials, such as CPP, W3G, and WAG, which enabled to achieve higher fixation strength even as early as 2-8 weeks after the insertion.

Animals↗