Interleukin-4 inhibition of osteoclast differentiation is stronger than that of interleukin-13 and they are equivalent for induction of osteoprotegerin production from osteoblasts.
Interleukin (IL)-4 and IL-13 are closely related cytokines known to inhibit osteoclast formation by targeting osteoblasts to produce an inhibitor, osteoprotegerin (OPG), as well as by directly targeting osteoclast precursors. However, whether their inhibitory actions are the same remains unclear. The inhibitory effect of IL-4 was stronger than that of IL-13 in an osteoclast-differentiation culture system containing mouse osteoblasts and osteoclast precursors. Both cytokines induced OPG production by osteoblasts in similar time- and dose-dependent manners. However, IL-4 was stronger in direct inhibition that targeted osteoclast precursors. Furthermore, IL-4 induced phosphorylation of signal transducer and activator of transcription-6 (STAT6) at lower concentrations than those of IL-13 in osteoclast precursors. IL-4 but not IL-13 strongly inhibited the expression of nuclear factor of activated T-cells, cytoplasmic 1 (nuclear factor-ATc1), a key factor of osteoclast differentiation, by those precursors. Thus, the activities of IL-4 and IL-13 toward osteoclast precursors were shown to be different in regards to inhibition of osteoclast differentiation, whereas those toward osteoblasts for inducing OPG expression were equivalent.
Yamada
Atsushi
A
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan.
Takami
Masamichi
M
Kawawa
Tadaharu
T
Yasuhara
Rika
R
Zhao
Baohong
B
Mochizuki
Ayako
A
Miyamoto
Yoichi
Y
Eto
Tomoo
T
Yasuda
Hisataka
H
Nakamichi
Yuko
Y
Kim
Nacksung
N
Katagiri
Takenobu
T
Suda
Tatsuo
T
Kamijo
Ryutaro
R
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D050778:NFATC Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053244:Osteoprotegerin / Q000096:biosynthesis* / Q000235:genetics; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050800:STAT6 Transcription Factor / Q000378:metabolism
D018793:Interleukin-13; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C505689:Tnfsf11 protein, mouse; D015847:Interleukin-4