Interleukin-6 modulates trabecular and endochondral bone turnover in the nude mouse by stimulating osteoclast differentiation.
A great deal of evidence has been accumulating that implicates the immune system in normal and pathological bone turnover. The objective of the present study was to examine the possible involvement of cytokines produced by T lymphocytes in bone metabolism. We have chosen the immunologically compromised athymic mouse, which demonstrate sclerotic features in its trabecular bone, as the animal model for assessment of possible modulation effects of interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) on bone and cartilage metabolism. The cytokines were applied by daily subcutaneous injections for 3 consecutive days. Histomorphometry, measuring epiphyseal trabecular bone volume (ETBV), metaphyseal trabecular bone volume (MTBV), and the width of the growth plate, and tartrate-resistant acid phosphatase (TRAP) histochemistry were used to assess parameters of bone turnover in the proximal tibia. IL-6, but not IL-1alpha, reduced ETBV and MTBV. Both IL-6 and IL-1alpha reduced the width of the growth plate. IL-6, but not IL-1alpha, increased the number of chondroclasts and osteoclasts in the primary spongiosa of the proximal tibia, as well as the number of nuclei. The resultant bone resembled that of the wild-type mouse. The results point to IL-6 as a possible regulator of bone turnover in vivo. It is suggested that the athymic mouse has a deficiency somewhere in the cascade of events leading to the production of IL-6 or, alternatively, that IL-6 replaces other factors that are supplied by T lymphocytes directly or indirectly. As T lymphocytes interact with B lymphocytes it is suggested that the athymic mouse might be appropriate for studying the in vivo effects of the immune system on normal bone metabolism.
Rozen
N
N
Department of Orthopedic Surgery A, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Ish-Shalom
S
S
Rachmiel
A
A
Stein
H
H
Lewinson
D
D
D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D002454:Cell Differentiation / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D002118:Calcium