title: Inhibitory regulation of osteoclast differentiation by interleukin-3 via regulation of c-Fos and Id protein expression.
abstract: Interleukin-3 (IL-3) is produced under various pathological conditions and is thought to be involved in the pathogenesis of inflammatory diseases; however, its function in bone homeostasis under normal conditions or nature of the downstream molecular targets remains unknown. Here we examined the effect of IL-3 on osteoclast differentiation from mouse and human bone marrow-derived macrophages (BMMs). Although IL-3 can induce osteoclast differentiation of multiple myeloma bone marrow cells, IL-3 greatly inhibited osteoclast differentiation of human BMMs isolated from healthy donors. These inhibitory effects of IL-3 were only observed at early time points (days 0 and 1). IL-3 inhibited the expression of c-Fos and NFATc1 in BMMs treated with RANKL. However, IL-3-mediated inhibition of osteoclast differentiation was not completely reversed by ectopic expression of c-Fos or NFATc1. Importantly, IL-3 induced inhibitor of DNA binding/differentiation (Id)1 in hBMMs, while Id2 were sustained during osteoclast differentiation of mBMMs treated with IL-3. Ectopic expression of NFATc1 in Id2-deficient BMMs completely reversed the inhibitory effect of IL-3 on osteoclast differentiation. Furthermore, inflammation-induced bone erosion was markedly inhibited by IL-3 administration. Taken together, our results suggest that IL-3 plays an inhibitory role in osteoclast differentiation by regulating c-Fos and Ids, and also exerts anti-bone erosion effects.
authors: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk, Korea.
authors: Jaemin
authors: J
authors: Oh
authors: Myeung Su
authors: MS
authors: Lee
authors: Jeong-Tae
authors: JT
authors: Yeon
authors: Sik-Won
authors: SW
authors: Choi
authors: Hun Soo
authors: HS
authors: Kim
authors: Hyeok
authors: H
authors: Shim
authors: Sam Youn
authors: SY
authors: Lee
authors: Byung Soo
authors: BS
authors: Youn
authors: Yoshifumi
authors: Y
authors: Yokota
authors: Jung Ha
authors: JH
authors: Kim
authors: Han Bok
authors: HB
authors: Kwak
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology; D011897:Random Allocation
chemical_list: C497450:ID2 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D007377:Interleukin-3; D051739:Microphthalmia-Associated Transcription Factor; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D016173:Macrophage Colony-Stimulating Factor