Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-κB and Akt pathways

Hu, Jin; Nishishita, Kazuhisa; Sakai, Eiko; Yoshida, Hajime; Kato, Yuzo; Tsukuba, Takayuki; Okamoto, Kuniaki

doi:10.1016/j.ejphar.2007.11.013

Cited by 134 publications

(90 citation statements)

References 32 publications

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“…Western blotting assays were done as described previously. 44 Anti-TRP53, anti-SQSTM1, and anti-CTSB antibodies were used as primary antibodies. Every experiment was repeated at least 3 times, and representative data are shown.…”

Section: Western Blot Analysismentioning

confidence: 99%

Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence

et al. 2016

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Macroautophagy/autophagy has profound implications for aging. However, the true features of autophagy in the progression of aging remain to be clarified. In the present study, we explored the status of autophagic flux during the development of cell senescence induced by oxidative stress. In this system, although autophagic structures increased, the degradation of SQSTM1/p62 protein, the yellow puncta of mRFP-GFP-LC3 fluorescence and the activity of lysosomal proteolytic enzymes all decreased in senescent cells, indicating impaired autophagic flux with lysosomal dysfunction. The influence of autophagy activity on senescence development was confirmed by both positive and negative autophagy modulators; and MTOR-dependent autophagy activators, rapamycin and PP242, efficiently suppressed cellular senescence through a mechanism relevant to restoring autophagic flux. By time-phased treatment of cells with the antioxidant N-acetylcysteine (NAC), the mitochondria uncoupler carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and ambroxol, a reagent with the effect of enhancing lysosomal enzyme maturation, we found that mitochondrial dysfunction plays an initiating role, while lysosomal dysfunction is more directly responsible for autophagy impairment and senescence. Interestingly, the effect of rapamycin on autophagy flux is linked to its role in functional revitalization of both mitochondrial and lysosomal functions. Together, this study demonstrates that autophagy impairment is crucial for oxidative stressinduced cell senescence, thus restoring autophagy activity could be a promising way to retard senescence.

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Section: Western Blot Analysismentioning

confidence: 99%

Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence

et al. 2016

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“…Bone marrow cells were prepared as previously described by Hu et al (22). For the experiments of osteoclastogenesis in bone marrow macrophages (BMMs), freshly prepared bone marrow cells were incubated in 100-mm standard dishes with α-MEM containing 10% FBS, as described above, in the presence of 10 ng/ml M-CSF (PeproTech, Rocky Hill, NJ, USA) for 1 day.…”

Section: Cell Culturementioning

confidence: 99%

Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells

et al. 2011

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Abstract.Recent research has shown that platinum nanoparticles (nano-Pt) efficiently quench reactive oxygen species (ROS) as a reducing catalyst. ROS have been suggested to regulate receptor activator of NF-κB ligand (RANKL)-stimulated osteoclast differentiation. In the present study, we examined the direct effects of platinum nano-Pt on RANKL-induced osteoclast differentiation of murine pre-osteoclastic RAW 264.7 cells. The effect of the nano-Pt on the number of osteoclasts was measured and their effect on the mRNA expression for osteoclast differentiation was assayed using real-time PCR. Nano-Pt appeared to have a ROS-scavenging activity. Nano-Pt decreased the number of osteoclasts (2+ nuclei) and large osteoclasts (8+ nuclei) in a dose-dependent manner without affecting cell viability. In addition, this agent significantly blocked RANKL-induced mRNA expression of osteoclastic differentiation genes such as c-fms, NFATc1, NFATc2, and DC-STAMP as well as that of osteoclast-specific marker genes including MMP-9, Cath-K, CLC7, ATP6i, CTR, and TRAP. Although nano-Pt attenuated expression of the ROS-producing NOXfamily oxidases, Nox1 and Nox4, they up-regulated expression of Nox2, the major Nox enzyme in macrophages. These findings suggest that the nano-Pt inhibit RANKL-stimulated osteoclast differentiation via their ROS scavenging property. The use of nano-Pt as scavengers of ROS that is generated by RANKL may be a novel and innovative therapy for bone diseases.

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“…2B and C). Our previous study showed that the inhibition of Akt suppressed phosphorylation of IκBα and NFκB DNAbinding activity, and blocked RANKL-induced osteoclastogenesis in mouse bone marrow macrophages (20).…”

Section: Discussionmentioning

confidence: 97%

Antitumor Effect of Temsirolimus against Oral Squamous Cell Carcinoma Associated with Bone Destruction

Okui

Shimo

Fukazawa

et al. 2010

Molecular Cancer Therapeutics

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The mammalian target of rapamycin (mTOR) is engaged in the molecular pathogenesis of oral squamous cell carcinoma, which frequently invades the maxilla or the mandible. However, the effects of a mTOR inhibitor on bone destruction associated with oral squamous cell carcinoma are still unclear. In this study, we investigated the antitumor effect of temsirolimus-mediated mTOR inhibition against advanced oral squamous cell carcinoma. Temsirolimus inhibited the proliferation and migration of HSC-2 oral squamous cell carcinoma cells in vitro and suppressed the growth of oral squamous cell carcinoma xenografts in vivo. Significantly, we clearly show that temsirolimus inhibited osteoclast formation both in vitro and in vivo. Reverse transcriptase-PCR analysis showed that temsirolimus decreased the mRNA expression of receptor activator for nuclear factor-κB ligand, known as an osteoclast differentiation factor in bone stromal ST2 cells. Moreover, temsirolimus normalized blood-free calcium concentration in mouse models for humoral hypercalcemia. These findings suggest that mTOR signaling is a potential target of oral squamous cell carcinoma associated with bone destruction, and hence we describe the efficacy of temsirolimus for the treatment of advanced oral squamous carcinoma. Mol Cancer Ther; 9(11); 2960-9. ©2010 AACR.

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Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-κB and Akt pathways

Cited by 134 publications

References 32 publications

Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence

Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence

Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells

Antitumor Effect of Temsirolimus against Oral Squamous Cell Carcinoma Associated with Bone Destruction

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