Abstract
Excessive bone resorption by osteoclasts causes bone loss-related diseases and reactive oxygen species (ROS) act as second messengers in intercellular signaling pathways during osteoclast differentiation. In this study, we explored the protective effects of fermented oyster extract (FO) against receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast differentiation in murine monocyte/macrophage RAW 264.7 cells. Our results showed that FO markedly inhibited RANKL-induced activation of tartrate-resistant acid phosphatase and formation of F-actin ring structure. Mechanistically, FO has been shown to down-regulate RANKL-induced expression of osteoclast-specific markers by blocking the nuclear translocation of NF-κB and the transcriptional activation of nuclear factor of activated T cells c1 (NFATc1) and c-Fos. Furthermore, FO markedly diminished ROS production by RANKL stimulation, which was associated with blocking the expression of nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) and its regulatory subunit Rac-1. However, a small interfering RNA (siRNA) targeting NOX1 suppressed RANKL-induced expression of osteoclast-specific markers and production of ROS and attenuated osteoclast differentiation as in the FO treatment group. Collectively, our findings suggest that FO has anti-osteoclastogenic potential by inactivating the NF-κB-mediated NFATc1 and c-Fos signaling pathways and inhibiting ROS generation, followed by suppression of osteoclast-specific genes. Although further studies are needed to demonstrate efficacy in in vivo animal models, FO may be used as an effective alternative agent for the prevention and treatment of osteoclastogenic bone diseases.
Highlights
Bone remodeling is a dynamic physiological response coupled with bone formation and resorption, and osteoclasts and osteoblasts have opposite roles in this process
We investigated the effect of fermented oyster extract (FO) on RANKL-mediated osteoclast differIennttihateiopnruesseinngt astRuAdWy, 2w64e.7icnevlel smtiogdateeld
As mentioned in many studies, several cellular signaling pathways for osteoclastogenesis are activated as downstream signals of the RANKL-RANK stimulus
Summary
Bone remodeling is a dynamic physiological response coupled with bone formation and resorption, and osteoclasts and osteoblasts have opposite roles in this process. When RAW 264.7 cells were treated with RANKL, the phosphorylation of PI3K, which is required for osteoclast survival and differentiation [33], was dramatically increased. According to the flow cytometry analysis shown, the ROS levels in RANKL-stimulated RAW 264.7 cells were markedly increased compared with the control group, and this effect was. We examined the effect of FO signoifinctahnetleyxpartteesnsiuoanteodf NinOtXh1e apnrdeseitnscreegouf laFtOor.yInsuabdudniitti,oRna, cN-1-a[c3e6t,3y7l ]c, yinsteRiAneN(KNLA-sCti)m, ualaptoedtenRtAW ROSceslclas.vAensgcearn, sbheowseeedncformompltehtee iinmhmibuitnioonblooftRaAnaNlyKsLis-msheodwianteidn RFOigSuraecc6uBm, NulOatXio1nparnodteoinsteexopclraesstsion formwaatsiodnr, asmugagtiecsatlilnygitnhdautciendhibbiytioRnAoNfKoLst,ewochlaicsht ddifefcerreeansteiadtiionnabycoFnOcemntaryatbioenm-deedpiaetneddetnhtromuagnhnaer in ROSthgeenperreasteionncebloofckFaOde.(Figure 6B) Consistent with this result, the increase in Rac-1 expression observed in cells treated with RANKL was greatly weakened by FO. A1Int(thNeinbOuitXaiot1en)saRonAfdNRNKaOcL1X-Ii1nndREuAxcepWdreEs2sx6ip4orn.e7ssCbiyoelnlsSomf NalilcoItnintearmfeirdeenAcedeRniNneAD(isniuRcNleAot)ideRPedhuocspeshaRteA(NNAKDL-PinHd)uced Osteoclastogenesis in RAW 264.7 Cells In the process of osteoclast differentiation by RANKL, the NOX family proteins play a critical role in produIcningprReOviSoubsy tsrtaundsifeesr,rinRgOeSleicstroanspfortoemnt NpAosDitPivHetoremguollaetcourlafroorxyogseteno[l3ca4s,3t5]d.iIfnfepreanrttiiacutiloanr, by NOXac1t-idveaptienngdNenOt XRO-1S[1g0e,n3e1r]a.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
