Local bone injections of LPS and M-CSF increase bone resorption by different pathways in vivo in rats.
We investigated the local in vivo action of lipopolysaccharide (LPS), a potent monocyte activator, and of macrophage colony-stimulating factor (M-CSF), a hemopoietic growth factor influencing monocyte differentiation, on bone resorption in normal female 8-wk-old rats. LPS (2 injections of 0.5 microgram), M-CSF (2 injections of either 12.5, 25, 100, or 500 ng), or vehicle was injected into bone marrow space through a thin catheter implanted, under hydrochloride anesthesia, in the distal end of the right femur. Histomorphometry was performed after staining of the tartrate-resistant acid phosphatase (TRAP). The number of osteoclasts and of TRAP-positive marrow cells (considered as osteoclast precursors) were counted in the secondary spongiosa. LPS caused a 3-fold increase in osteoclast surface, a 4.5-fold increase in the number of osteoclasts, but no change in the number of TRAP-positive marrow cells. M-CSF induced a striking dose-dependent biphasic effect on the number of TRAP-positive marrow cells and on bone resorption (no change with the lowest or with the highest concentrations, although the two intermediate doses significantly increased resorption surfaces and the number of osteoclasts). Our results demonstrate a local in vivo effect of LPS and of M-CSF on bone resorption and suggest that these substances act at different stages of osteoclast development and function.
Orcel
P
P
Institut National de la Santé et de la Recherche Médicale Unité 349, Centre Viggo Petersen, Paris, France.
Feuga
M
M
Bielakoff
J
J
De Vernejoul
M C
MC
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D007267:Injections; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D002118:Calcium