Effects of IL-23 and IL-27 on osteoblasts and osteoclasts: inhibitory effects on osteoclast differentiation.
Interleukin (IL)-23 and IL-27 are IL-6/IL-12 family members that play a role in the regulation of T helper 1 cell differentiation. Cytokines are known to be involved in the bone remodeling process, although the effects of IL-23 and IL-27 have not been clarified. In this study, we examined the possible roles of these cytokines on osteoblast phenotypes and osteoclastogenesis. We found that IL-27 induced signal transducers and activators of transcription 3 activation in osteoblasts. However, neither IL-23 nor IL-27 showed any significant effects on alkaline phosphatase activity, receptor activator of nuclear factor kappaB ligand (RANKL) expression, mRNA expression such as alkaline phosphatase type I procollagen, or the proliferation of osteoblasts. Osteoclastogenesis from bone marrow cells induced by soluble RANKL was partially inhibited by IL-23 and IL-27 with reduced multinucleated cell numbers, but these interleukins did not affect the proliferation of osteoclast progenitor cells. These results indicate that IL-23 and IL-27 could partly modify cell fusion or the survival of multinucleated osteoclasts. On the other hand, partially purified T cells, which are activated by 2 microg/ml anti-CD3 antibody, completely inhibited osteoclastogenesis by M-CSF/RANKL. On using T cells activated with 0.2 microg/ml anti-CD3 antibody, in which osteoclastogenesis was partially inhibited, the interleukins had additive effects for inhibiting osteoclastogenesis. Although the consequences of phosphorylated signals in osteoblasts have not been identified, IL-23 and IL-27, partly and indirectly through activated T cells, inhibited osteoclastogenesis, indicating that these interleukins may protect against bone destructive autoimmune disorders.
Kamiya
Sadahiro
S
Department of Clinical Sciences, Josai International University, 1 Gumyo, Togane, Chiba 283-8555, Japan. kamiyas@jiu.ac.jp
Nakamura
Chika
C
Fukawa
Takeshi
T
Ono
Katsuhiro
K
Ohwaki
Toshiyuki
T
Yoshimoto
Takayuki
T
Wada
Seiki
S
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D005994:Glycerophosphates / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000494:pharmacology*; D053759:Interleukin-23 / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D005994:Glycerophosphates; D020381:Interleukin-17; D053759:Interleukin-23; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018123:Receptors, Interleukin; D007371:Interferon-gamma; D001205:Ascorbic Acid; C031463:beta-glycerophosphoric acid
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