1 / 26

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

kenaz
Télécharger la présentation

TNF-alpha activates osteoclasts independent of and Synergistic with RANKL

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related