In vivo administration of recombinant TNF-alpha promotes bone resorption in mice.
BACKGROUND
In vitro studies demonstrated that proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) modulates bone metabolism.


OBJECTIVE
The aim of our study was to confirm the ability of TNF-alpha to induce osteoclastogenesis and bone resorption in an in vivo experiment, with the use of calvarial model in mice.


METHODS
Twenty C57-Black mice were divided into four groups with five animals in each. The first group was infused subcutaneously on their back with recombinant mouse (rm) TNF-alpha via osmotic minipumps for 3 d, the second group was similarly infused with phosphate-buffered saline (PBS), the third group was infused with rmTNF-alpha to the region above the parietal bone and the fourth group with PBS in the same manner. Number of osteoclasts on parietal bone was determined morphometrically. Serum calcium and phosphates were monitored colorimetrically.


RESULTS
Serum calcium level and number of osteoclasts on parietal bone were significantly greater after infusion of rmTNF-alpha above the parietal bone, whereas after subcutaneous delivery these parameters were similar to the control group.


CONCLUSIONS
We are concluding that TNF-alpha has the ability to change the bone metabolism in a paracrine manner only.
Gaspersic
Rok
R
Department of Oral Medicine and Periodontology, Institute of Histology and Embryology, Faculty of Medicine, University of Ljubljana and Clinical Institute of Clinical Chemistry and Biochemistry, Clinical Centre, Ljubljana, Slovenia.
Stiblar-Martincic
Draga
D
Osredkar
Josko
J
Skaleric
Uros
U
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced* / Q000473:pathology; D002118:Calcium / Q000097:blood; D002452:Cell Count; D007091:Image Processing, Computer-Assisted; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D019899:Paracrine Communication; D010294:Parietal Bone / Q000187:drug effects / Q000473:pathology; D010710:Phosphates / Q000097:blood; D010919:Placebos; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects*
D010710:Phosphates; D010919:Placebos; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium