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TNF-alpha activates osteoclasts independent of and Synergistic with RANKL

TNF-alpha activates osteoclasts independent of and Synergistic with RANKL. Susannah A. Hill. Background. Recent research has implicated RANKL as the strongest cytokine precursor of osteoclasts. Can TNF-alpha upregulate osteoclasts without RANKL?. 3 Studies. Compare TNF-alpha to RANKL

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TNF-alpha activates osteoclasts independent of and Synergistic with RANKL

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  1. TNF-alpha activates osteoclasts independent of and Synergistic with RANKL Susannah A. Hill

  2. Background

  3. Recent research has implicated RANKL as the strongest cytokine precursor of osteoclasts

  4. Can TNF-alpha upregulate osteoclasts without RANKL?

  5. 3 Studies Compare TNF-alpha to RANKL Evaluate TNF-alpha alone Analyze the synergism among the two cytokines

  6. The authors compared the cytokines both in-vitro and ex-vivo

  7. In order to measure osteoclastogenesis, actin ring formation was quantitated

  8. A comparison of in-vitro and ex-vivo preparations of bone cells treated with either TNF-alpha or RANKL • TNF-alpha was equipotent with RANKL in actin ring formation • The two cytokines are nearly equipotent in both an in-vitro and ex-vivo enviornment

  9. TNF-alpha and RANKL consistently display equipotent upregulation of osteoclasts Induction of osteoclastic differentiation and function by TNF-alpha and RANKL

  10. TNF-alpha

  11. How effective is TNF-alpha in the absence of RANKL?

  12. TNF-alpha directly stimulates osteoclast spread area This shows that osteoclasts are resonding directly to TNF-alpha

  13. Photomicrographs of in-vitro bone cells with or without the presence of TNF-alpha • The upregulation of actin ring formation is dependent upon the concentration of TNF-alpha

  14. These results indicate that TNF-alpha is capable of working independently

  15. A stain for TRAP (tartrate acid phosphatase) identifies active osteoclasts

  16. TRAP secretion

  17. Marrow cells take on the form of osteoclasts after treatment with TNF-alpha TNF-alpha induces osteoclastic differentiation in bone marrow cells

  18. TNF-alpha causes multinuclear cells to differentiate into osteoclasts in spleen cells

  19. Whole bone cultures treated with TNF-alpha show evidence of excavation of bone surface

  20. Electron micrograph of bone marrow cells after a 12 day incubation with TNF-alpha

  21. These results indicate that TNF-alpha is capable of working independently

  22. Does TNF-alpha work together with RANKL?

  23. Actin ring formation is significantly increased when both RANKL and TNF-alpha are applied TNF alpha potently synergizes with RANKL

  24. TNF-alpha synergizes with RANKL for the induction of actin rings in osteoclasts

  25. Conclusions TNF-alpha is equipotent to RANKL TNF-alpha is able to work independently TNF-alpha and RANKL synergize to increase the rate of osteoclastic bone resorbtion

  26. Why is it important to investigate the precursors for bone resorbtion? • Post-menopausal osteoporosis • Joint failure • Prosthetic-induced osteolysis

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