Fish oil suppresses bone resorption by inhibiting osteoclastogenesis through decreased expression of M-CSF, PU.1, MITF and RANK in ovariectomized rats

Nakanishi, Atsuko; Tsukamoto, Ikuyo

doi:10.3892/mmr.2013.1446

Cited by 27 publications

(17 citation statements)

References 45 publications

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“…However, long-term estrogen replacement therapy can increase the risk of endometrial and breast cancers. Therefore, many investigators have focused their efforts on developing a new anti-resorptive agent that does not have side effects [7]–[10]. Because osteoclasts function in bone resorption, specifically inhibiting osteoclasts has been considered the main target in numerous studies.…”

Section: Introductionmentioning

confidence: 99%

Acteoside Suppresses RANKL-Mediated Osteoclastogenesis by Inhibiting c-Fos Induction and NF-κB Pathway and Attenuating ROS Production

Lee

et al. 2013

PLoS ONE

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Numerous studies have reported that inflammatory cytokines are important mediators for osteoclastogenesis, thereby causing excessive bone resorption and osteoporosis. Acteoside, the main active compound of Rehmannia glutinosa, which is used widely in traditional Oriental medicine, has anti-inflammatory and antioxidant potentials. In this study, we found that acteoside markedly inhibited osteoclast differentiation and formation from bone marrow macrophages (BMMs) and RAW264.7 macrophages stimulated by the receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL). Acteoside pretreatment also prevented bone resorption by mature osteoclasts in a dose-dependent manner. Acteoside (10 µM) attenuated RANKL-stimulated activation of p38 kinase, extracellular signal-regulated kinases, and c-Jun N-terminal kinase, and also suppressed NF-κB activation by inhibiting phosphorylation of the p65 subunit and the inhibitor κBα. In addition, RANKL-mediated increases in the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and in the production of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were apparently inhibited by acteoside pretreatment. Further, oral acteoside reduced ovariectomy-induced bone loss and inflammatory cytokine production to control levels. Our data suggest that acteoside inhibits osteoclast differentiation and maturation from osteoclastic precursors by suppressing RANKL-induced activation of mitogen-activated protein kinases and transcription factors such as NF-κB, c-Fos, and NFATc1. Collectively, these results suggest that acteoside may act as an anti-resorptive agent to reduce bone loss by blocking osteoclast activation.

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Section: Introductionmentioning

confidence: 99%

Acteoside Suppresses RANKL-Mediated Osteoclastogenesis by Inhibiting c-Fos Induction and NF-κB Pathway and Attenuating ROS Production

Lee

et al. 2013

PLoS ONE

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“…However, there was no significant effect of n-3 PUFA on the bone expression of RANKL or its decoy receptor OPG, which are also important determinants of osteoclastic differentiation and activation (5) . Previous in vitro and in vivo studies examining the effects of n-3 PUFA on the RANKL/OPG pathway reported mixed results (32)(33)(34) . Sacco et al (35) reported that shortterm (2 weeks) periods of n-3 PUFA (flaxseed oil) supplementation resulted in no changes in the serum level of RANKL or in the OPG:RANKL ratio in OVX rats, but that E 2 treatment did result in such changes.…”

Section: Discussionmentioning

confidence: 99%

Synergistic attenuation of ovariectomy-induced bone loss by combined use of fish oil and 17β-oestradiol

2017

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Oestrogen and n-3 PUFA, especially EPA and DHA, have been reported to have beneficial effects on bone loss. Thus, the purpose of the present study was to investigate the synergistic bone-protective mechanism of combined treatments of EPA+DHA supplementation and oestrogen injection in ovariectomised rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0 %, 1 % or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and after a 1-week recovery period rats were injected with either 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Combined use of n-3 PUFA and E2 synergistically increased femoral cortical bone volume, bone mineral content and the bone expression of runt-related transcription factor 2 (RUNX2), but decreased the bone expression of IL-1β. Both n-3 PUFA and E2 decreased the bone expressions of IL-7, TNF-α and PPAR-γ, and increased the bone expression of oestrogen receptor-α. n-3 PUFA in the presence of E2 and E2 alone significantly decreased the bone expressions of IL-1β and IL-6 and increased the bone expression of RUNX2. E2 significantly decreased the serum levels of bone turnover markers and the bone expression of receptor activator of NF-κB ligand, but decreased the bone expression of osteoprotegerin. The combined use of n-3 PUFA and E2 exerted synergistic bone-protective efficacy through up-regulation of RUNX2, an essential transcription factor for bone formation, as well as the suppression of bone-resorbing cytokine IL-1β.

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“…However, the underlying mechanism is still not completely understood. MITF and its co-activator PU.1 have recently been designated as a reliable target responsible for osteoclastogenic disorders [13]. It is known that osteoclasts shared a common origin with preadipocytes, but they were mutually exclusive with each other in the differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…There was tight synergy in the transcription of those genes and/or modulation of their downstream genes. For these reasons, MITF and PU.1 are regarded as a target for treatment of osteopathic conditions, such as bone resorption and osteopetrosis [13]. …”

Section: Introductionmentioning

confidence: 99%

MITF and PU.1 inhibit adipogenesis of ovine primary preadipocytes by restraining C/EBPβ

Ruan

et al. 2017

Cell Mol Biol Lett

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BackgroundPU box-binding protein (PU.1) is a master gene of hematopoietic lineage and an important specific transcription factor in osteoclast lineage. There is proof of its expression in adipose tissue, and it is known to significantly and negatively affect adipogenesis. However, it is unclear whether there are any other molecules involved in this process.MethodsWe wished to explore the effect of PU.1’s co-activator microphthalmia-associated transcription factor (MITF) on the adipogenic differentiation of ovine primary preadipocytes. The expression vectors pcDNA-MITF and pcDNA-PU.1, and MITF siRNA and PU.1 siRNA were transfected or co-transfected into ovine tail primary preadipocytes. Real-time PCR and western blot analysis were applied to investigate the expression levels of PU.1 and MITF. The morphologic changes in the cells were observed under a microscope at a magnification of × 200 after staining with Oil Red O. The triglyceride (TG) content in cells was also determined after transfection.ResultsMITF and its co-activator PU.1 synergistically exhibited an opposite expression pattern to that of CCAAT-enhancer-binding protein-β (C/EBPβ) during adipogenic differentiation of ovine primary preadipocytes. Before induction of differentiation, overexpression of MITF or PU.1 inhibited the expression of C/EBPβ and adipogenesis in the cells; and knockdown of MITF or PU.1 promoted the expression of C/EBPβ and adipogenesis in the cells. The inhibitory or promotive effect was enhanced when MITF and PU.1 were co-overexpressed or co-silenced. However, when MITF and/or PU.1 were overexpressed after day 2 of differentiation, no changes in adipogenesis of the cells were observed.ConclusionsMITF and its co-activator PU.1 inhibited adipogenesis of ovine primary preadipocytes by restraining C/EBPβ.Electronic supplementary materialThe online version of this article (doi:10.1186/s11658-016-0032-y) contains supplementary material, which is available to authorized users.

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Fish oil suppresses bone resorption by inhibiting osteoclastogenesis through decreased expression of M-CSF, PU.1, MITF and RANK in ovariectomized rats

Cited by 27 publications

References 45 publications

Acteoside Suppresses RANKL-Mediated Osteoclastogenesis by Inhibiting c-Fos Induction and NF-κB Pathway and Attenuating ROS Production

Acteoside Suppresses RANKL-Mediated Osteoclastogenesis by Inhibiting c-Fos Induction and NF-κB Pathway and Attenuating ROS Production

Synergistic attenuation of ovariectomy-induced bone loss by combined use of fish oil and 17β-oestradiol

MITF and PU.1 inhibit adipogenesis of ovine primary preadipocytes by restraining C/EBPβ

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