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1.
Fiziol Zh (1994) ; 59(2): 47-51, 2013.
Article in Ukrainian | MEDLINE | ID: mdl-23821937

ABSTRACT

Our purpose was to investigate the oxygen partial pressure changes on the osteometric and biochemical markers of bone tissue in rats. It was shown that breathing of altered gas mixture did not change the mass, general length, sagittal diameter and density thigh-bones in 12-month Wistar male-rats. The dosed normobaric hypoxia increased the activity of alkaline phosphatase and decreased the activity of tartrate-resistant acid phosphatase. At the same time normobaric hyperoxia with 40 and 90% oxygen conversely decreased the activity of alkaline phosphatase and increased the activity of tartrate-resistant acid phosphatase.


Subject(s)
Bones of Lower Extremity/anatomy & histology , Hypoxia/physiopathology , Oxygen/metabolism , Acid Phosphatase/metabolism , Alkaline Phosphatase/metabolism , Animals , Bone Density/physiology , Bone Regeneration/physiology , Bones of Lower Extremity/enzymology , Hypoxia/enzymology , Isoenzymes/metabolism , Male , Partial Pressure , Rats , Rats, Wistar , Tartrate-Resistant Acid Phosphatase
2.
Cytokine ; 38(3): 151-6, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17689092

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the expression of several cytokines, matrix metalloproteinases (MMPs), and tissue inhibitor of matrix metalloproteinases (TIMP)-1 in osteoarthritis (OA) and control sera and different joint tissues. METHODS: Serum, synovial fluid, cartilage, synovial and subchondral bone tissues were examined in OA and control subjects. The protein level of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-8, IL-10 and MMP-2, MMP-3, MMP-9, and TIMP-1 were measured by immunoanalysis. RESULTS: Serum levels of TNF-alpha, MMP-3 and -9 were significantly higher in OA patients than in controls. Conversely, serum IL-10 was decreased in OA patients. CRP was elevated when compared to healthy controls and decreased significantly 6 months after the surgery. In contrast to control samples, OA cartilage and synovium revealed significantly higher MMP-2, -3, -9 and IL-10. IL-1alpha was significantly higher in OA cartilage and IL-8 in OA synovium. Interestingly, MMP-3, -9, TIMP-1 and all tested cytokines were up-regulated in OA subchondral bone. DISCUSSION: This study demonstrates pro-inflammatory condition of OA pathology and supports the idea that vascularized subchondral region may increase the synthesis of cytokines and MMPs leading to degradation of adjacent cartilage.


Subject(s)
Bones of Lower Extremity/enzymology , Bones of Lower Extremity/immunology , Cytokines/metabolism , Matrix Metalloproteinases/metabolism , Osteoarthritis, Hip/enzymology , Osteoarthritis, Hip/immunology , Aged , C-Reactive Protein/metabolism , Cartilage, Articular/enzymology , Cartilage, Articular/immunology , Case-Control Studies , Cytokines/blood , Female , Humans , Inflammation Mediators/blood , Inflammation Mediators/metabolism , Male , Matrix Metalloproteinases/blood , Middle Aged , Osteoarthritis, Hip/surgery , Synovial Fluid/enzymology , Synovial Fluid/immunology
3.
J Pharmacol Exp Ther ; 317(3): 1044-53, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16501068

ABSTRACT

Mitogen-activated protein kinase (MAPK) pathways are implicated in joint destruction in rheumatoid arthritis (RA) by modulating the production and functions of inflammatory cytokines. Although p38 MAPK (p38) participates in signaling cascades leading to osteolysis in arthritis, the mechanisms of its action in this process remain incompletely understood. Here, we found that the osteoclast (Ocl) precursors expressed p38alpha, but not p38beta, p38delta, and p38gamma isoforms. Treatment of these cells with receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) resulted in p38 activation. Importantly, Ocl development induced by RANKL or RANKL and tumor necrosis factor (TNF)-alpha was blocked with the novel p38 inhibitor 4-(3-(4-chlorophenyl)-5-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyrimidine (SC-409). To validate in vitro data, p38 role was further investigated in streptococcal cell wall (SCW)-induced arthritis in rats. We found that SCW-induced joint swelling and bone destruction were attenuated by SC-409. Mechanistically, the data show that SCW-stimulated DNA binding activity of the transcription factor myocyte-enhancing factor 2 C, which is downstream of p38, was inhibited by SC-409. In addition, SC-409 inhibited SCW-stimulated expression of numerous factors, including TNF-alpha, interleukin-1beta, and RANKL. Although c-Jun NH2-terminal kinase and NF-kappaB pathways were activated in vitro by RANKL and in vivo by SCW, SC-409 had no significant effect on these pathways. In conclusion, our data show that p38 modulates the production and signaling of cytokines, thus providing a mechanism of the bone-sparing effect of SC-409 in rat arthritis. These data present SC-409 as a novel potent p38 inhibitor and suggest that p38-based therapies may be beneficial in preventing bone loss associated with RA.


Subject(s)
Arthritis, Experimental/prevention & control , Osteoclasts/drug effects , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Animals , Arthritis, Experimental/enzymology , Arthritis, Experimental/pathology , Bones of Lower Extremity/drug effects , Bones of Lower Extremity/enzymology , Bones of Lower Extremity/pathology , Carrier Proteins/pharmacology , Cell Line , Cytokines/biosynthesis , Female , Humans , Membrane Glycoproteins/pharmacology , Mice , Molecular Structure , Osteoclasts/enzymology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , RANK Ligand , Rats , Rats, Inbred Lew , Receptor Activator of Nuclear Factor-kappa B , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors
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