Quercetin, a potent suppressor of NF-κB and Smad activation in osteoblasts

Abstract

Abstract. Osteoclasts, the bone resorbing cells of the body, form when osteoclast precursors are exposed to the key osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL), a process requiring induction of NF-κB signaling. Quercetin is a ubiquitous plant-derived flavonoid with well documented antiinflammatory properties, in part, a consequence of its capacity to downmodulate the NF-κB signal transduction pathway. Consistent with this mechanism of action quercetin is reported to suppress osteoclastogenesis in vitro and prevent bone loss in ovariectomized mice in vivo. By contrast, the effect of quercetin on osteoblasts, the cells responsible for bone formation, is contradictory with conflicting reports of inhibition as well as stimulation. Given our previous reports that NF-κB antagonists promote osteoblast differentiation and activity, we compared the effects of quercetin on osteoclast and osteoblast differentiation and on NF-κB signal transduction in vitro. As expected, quercetin potently suppressed osteoclastogenesis and NF-κB activation induced by RANKL in osteoclast precursors. However, the same doses of quercetin had no effect on osteoblast mineralization, and failed to significantly alleviate the inhibitory effect of NF-κB-induced by TNFα, even though quercetin potently suppressed NF-κB activation in these cells. This apparent contradiction was explained by the fact that addition to its anti-NF-κB activity, quercetin also potently antagonized both TGFβ and BMP-2-induced Smad activation in osteoblast precursors. Taken together our data suggest that multiple competing actions of quercetin mediate both stimulatory and inhibitory actions on osteoblasts with the final physiological effect likely a function of the net balance between these stimulatory and inhibitory effects.

Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma

“…This study corroborates other previous studies on the anti-inflammatory and antiallergic properties of Allium cepa L. and quercetin [ 16 - 19 , 25 ], which might be linked to the ability of AcE an quercetin in down-modulate inflammatory processes through different signaling pathways such as NF-κB [ 43 - 45 ]. On the other hand, some authors discuss allergic reaction to onion.…”

Allium cepaL. and Quercetin Inhibit RANKL/Porphyromonas gingivalisLPS-Induced Osteoclastogenesis by Downregulating NF-κB Signaling Pathway

“…Of these products, flavonoids contained in fruits and vegetables have been found to be very active as anti-inflammatory agents [ 18 ]. The major flavonoid found in Allium cepa L. (onion) is quercetin (Qt) which exhibits many pharmacological properties such as anti-inflammatory and antioxidant effects [ 19 – 21 ]. Qt is also a potent inhibitor of in vitro osteoclastic differentiation [ 22 ].…”

Suppression of NF-κB Activation By Gentian Violet Promotes Osteoblastogenesis and Suppresses Osteoclastogenesis

“…TNFα further antagonizes BMP signaling by upregulating Smad ubiquitination regulatory factor 1 (Smurf1), promoting proteasomal degradation of bone morphogenetic signaling proteins [42]. Consistent with this data we have reported that multiple suppressors of NF-κB activation including the carotenoid beta-cryptoxanthin [43], the biphenol honokiol [19], vitamin K 2 [9], quercetin [20], zinc [24] and a pharmacological NF-κB inhibitor based on the NEMO binding domain [1] are all capable of rescuing the inhibitory effect of TNFα on BMP2 and/or TGFβ-induced Smad activation.…”

“…Interestingly, we have recently reported that several natural compounds, long believed to possess anabolic and/or anti-catabolic properties, may protect bone by antagonizing NF-κB activation. Among these agents are vitamin K 2 [9], 17beta-estradiol [17], the carotene, p-hydroxycinnamic acid, the xanthophyll, beta-cryptoxanthin [18], honokiol, a component of Asian herbal teas used extensively in traditional Japanese and Chinese medicine [19], and the plant-derived flavonoid quercetin [20]. …”