Alpha‐Lipoic Acid Promotes Osteoblastic Formation in H₂O₂‐Treated MC3T3‐E1 Cells and Prevents Bone Loss in Ovariectomized Rats

Abstract

Alpha-lipoic acid (ALA), a naturally occurring compound and dietary supplement, has been established as a potent antioxidant that is a strong scavenger of free radicals. Recently, accumulating evidences has indicated the relationship between oxidative stress and osteoporosis (OP). Some studies have investigated the possible beneficial effects of ALA on OP both in vivo and in vitro; however, the precise mechanism(s) underlying the bone-protective action of ALA remains unclear. Considering this, we focused on the anti-oxidative capacity of ALA to exert bone-protective effects in vitro and in vivo. In the present study, the effects of ALA on osteoblastic formation in H(2)O(2) -treated MC3T3-E1 pre-osteoblasts and ovariectomy (OVX)-induced bone loss in rats were investigated. The results showed that ALA promoted osteoblast differentiation, mineralization and maturation and inhibited osteoblast apoptosis, thus increasing the OPG/receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) ratio and leading to enhanced bone formation in vitro and inhibited bone loss in vivo. Further study revealed that ALA exerted its bone-protective effects by inhibiting reactive oxygen species (ROS) generation by down-regulating Nox4 gene expression and protein synthesis and attenuating the transcriptional activation of NF-κB. In addition, ALA might exert its bone-protective effects by activating the Wnt/Lrp5/β-catenin signaling pathway. Taken together, the present study indicated that ALA promoted osteoblastic formation in H(2)O(2) -treated MC3T3-E1 cells and prevented OVX-induced bone loss in rats by regulating Nox4/ROS/NF-κB and Wnt/Lrp5/β-catenin signaling pathways, which provided possible mechanisms of bone-protective effects in regulating osteoblastic formation and preventing bone loss. Taken together, the results suggest that ALA may be a candidate for clinical OP treatment.

Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

“…Our observation from the current study and data from other experiments (Fu et al, 2015) demonstrate that ovariectomy results in an elevation of Nox4 gene expression and protein synthesis as well as an increase in ROS production. Considering that FLL could scavenge free radical oxygen (Jeong et al, 2016) and elevate antioxidant enzyme levels in human neuroblastoma SH-SY5Y cells (Ju et al, 2012), we then investigated whether FLL exhibited antioxidant activities in osteoporotic rats.…”

“…In the previous study, we demonstrated that treatment of OVX rats with FLL markedly improved bone mechanical strength and bone microarchitectures (Guo et al, 2016a). Moreover, inhibition of Nox4 activity and expression further contributed to protection of osteoblasts against H 2 O 2 insults and prevention of OVX-induced bone loss (Fu et al, 2015). Therefore, the findings of the current study may suggest that FLL exhibits bone protective effect through inhibiting ROS release via the regulation of Nox4 expression in OVX rats.…”

“…However, little is known about the effect of FLL on oxidative stress in OVX rats. In fact, Nox4 is widely expressed in bone (Fu et al, 2015) and uteri (Fletcher et al, 2014). Additionally, FLL has been demonstrated to exhibit antioxidant activity in vitro (Chen et al, 2013).…”

Cytoprotective effect of chlorogenic acid against hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells through PI3K/Akt-mediated Nrf2/HO-1 signaling pathway

“…H 2 O 2 , as involvement of oxidative stress, may induce the self-generation of free radicals and produce a wide range of damages including apoptosis, necrosis or autophagy of various types of cells, including osteoblast cells [26–28]. In this study, MC3T3-E1 cells were exposed to H 2 O 2 to perform a model of oxidative damage, we found that treating MC3T3-E1 cells with H 2 O 2 resulted in reduction of cell viability, ROS production and apoptosis.…”

Alpha-Lipoic Acid Alleviates High-Glucose Suppressed Osteogenic Differentiation of MC3T3-E1 Cells via Antioxidant Effect and PI3K/Akt Signaling Pathway

“…The cells were subsequently divided into 4 experimental groups [19, 20]: (1) the control group: normal glucose (5.5 mM) α-MEM alone (NG), (2) the high glucose group: high glucose (25.5 mM) α-MEM alone (HG), (3) the 0.1 mM ALA group: high glucose α-MEM + 0.1 mM ALA (HG+) and (4) the 0.2 mM ALA group: high glucose α-MEM + 0.2 mM ALA (HG++).…”