Chemokines

Cure Arthritis Naturally

Cure Arthritis Naturally

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Chemokines are small heparin-binding cytoki-nes that were originally identified as chemo-tactic factors. Because of the presence of distinct N-terminal cysteine (C) residues, the chemokines are classified as C, CX3C, or CC. The roles played by chemokines in neutrophil activation and chemotaxis in inflammatory arthritis are well established, but their involvement in OA is less clear. When chondrocytes are activated by IL-1, TNF-a, IL-17, IL-18, or OSM, they express several chemokines. They also have receptors that cause responses that are associated with cartilage catabolism (for review see [30,71]. Borzi et al [29] were the first to report the expression of functional chemokine receptors (CCR1, CCR2, CCR3, CCR5, CXCR1, and CXCR2) on chondrocytes. The receptors, in interacting with their corresponding ligands, MCP-1, Regulated on Activation Normal T-cell

Expressed and Secreted (RANTES), and GROa, caused upregulation of MMP-3. Subsequent studies showed that IL-1^ and TNF-a increase the expression of the C-C chemokines, MCP-1, MIP-1a, MIP-1P, and RANTES, in normal and OA chondrocytes, and that RANTES increased expression of its own receptor, CCR5. MCP-1 and RANTES, in addition to increasing MMP-3 expression, inhibit proteoglycan synthesis and enhance proteoglycan release from the chondrocytes. The RANTES receptors CCR3 and CCR5, but not CCR1, are expressed in normal cartilage, whereas all three receptors are expressed in OA cartilage or after stimulation of normal chondrocytes by IL-1^. Furthermore, RANTES induces the expression of iNOS, IL-6, and MMP-1. More recent work has demonstrated the expression of an additional chemokine receptor, CXCR4, by chondrocytes, but not by synovial fibroblasts. Its ligand, stromal cell-derived factor 1 (SDF-1), occurs in high concentration in RA and OA synovial fluids [104]. SDF-1 and several other cytokines increase the synthesis of S100A, N-acetyl-b-d-glucuronidase, cathepsin B, and several MMPs in chondrocytes and induce DNA synthesis, cell proliferation [139], and PGE2 production [137]. Osteoarthritis chondrocytes in contact with autologous T lymphocytes produce enhanced levels of MMP-1, -3, and -13 and RANTES [155]. Furthermore, fibronectin fragments increase the expression of several chemokines by a partially NF-kB dependent mechanism [177]. Thus, in addition to recruiting leukocytes to sites of inflammation in arthritic joints and mediating synovial fibroblast responses and actions, chemokines modulate chondrocyte functions associated with cartilage degradation.

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Osteoarthritis

Osteoarthritis

Thank you for deciding to learn more about the disorder, Osteoarthritis. Inside these pages, you will learn what it is, who is most at risk for developing it, what causes it, and some treatment plans to help those that do have it feel better. While there is no definitive “cure” for Osteoarthritis, there are ways in which individuals can improve their quality of life and change the discomfort level to one that can be tolerated on a daily basis.

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