IL-6 is produced by osteoblasts and induces bone resorption.
To examine the possible involvement of IL-6 in bone metabolism, a mouse osteoblastic cell line (MC3T3-E1) and primary osteoblast-like cells from fetal mouse calvaria were cultured with several systemic and local bone-resorbing agents and their expression of IL-6 mRNA was determined. Local bone-resorbing agents such as IL-1 alpha, IL-1 beta, TNF-alpha, and LPS greatly induced IL-6 mRNA expression in both MC3T3-E1 cells and primary osteoblast-like cells. Parathyroid hormone slightly increased expression of IL-6 mRNA in primary osteoblast-like cells but not in MC3T3-E1 cells. Neither IL-6 nor 1 alpha,25-dihydroxyvitamin D3 increased expression of IL-6 mRNA in either of the osteoblast-like cells. In agreement with the expression of IL-6 mRNA, biologically active IL-6 was produced in response to the treatment with IL-1 alpha, TNF-alpha, and LPS in MC3T3-E1 cells. Adding IL-6 dose dependently stimulated the release of 45Ca from prelabeled fetal mouse calvaria. Simultaneously adding suboptimal concentrations of IL-6 and IL-1 alpha induced bone resorption cooperatively. In accord with the increase in the release of 45Ca by IL-6, there were three times as many osteoclasts in the bone sections of calvaria cultured with IL-6 for 5 days as in the controls. IL-6 slightly suppressed alkaline phosphatase activity and collagen synthesis in MC3T3-E1 cells. These results indicate that IL-6 is also produced by osteoblasts, preferentially in response to local bone-resorbing agents, and it induces bone resorption both alone and in concert with other bone-resorbing agents.
Ishimi
Y
Y
Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
Miyaura
C
C
Jin
C H
CH
Akatsu
T
T
Abe
E
E
Nakamura
Y
Y
Yamaguchi
A
A
Yoshiki
S
S
Matsuda
T
T
Hirano
T
T
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D005260:Female; D006131:Growth Inhibitors; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C050979:monocyte-macrophage differentiation factor; D003094:Collagen; D000469:Alkaline Phosphatase