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

• Published in: Journal of cellular physiology Vol. 230; no. 9; pp. 2184 - 2201
• Main Authors: Fu, Chao, Xu, Dong, Wang, Chang-Yuan, Jin, Yue, Liu, Qi, Meng, Qiang, Liu, Ke-Xin, Sun, Hui-Jun, Liu, Mo-Zhen
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.09.2015; Wiley Subscription Services, Inc
• Subjects: Animals; Antioxidants; Apoptosis; Apoptosis - drug effects; Biocompatibility; Biomedical materials; Bone growth; Bone loss; Bone Resorption - drug therapy; Bone Resorption - pathology; Catenin; Cell Differentiation - drug effects; Female; Free Radical Scavengers - administration & dosage; Free radicals; Gene expression; Humans; Hydrogen peroxide; Hydrogen Peroxide - administration & dosage; In vivo methods and tests; Lipoic acid; LRP5 protein; Mineralization; NF-κB protein; NOX4 gene; NOX4 protein; Osteoblastogenesis; Osteoblasts; Osteoblasts - drug effects; Osteogenesis; Osteogenesis - drug effects; Osteoporosis; Osteoporosis - drug therapy; Osteoporosis - pathology; Osteoprotegerin; Ovariectomy; Oxidative stress; Protein biosynthesis; Protein synthesis; RANK Ligand - biosynthesis; Rats; Reactive oxygen species; Rodents; Signal transduction; Signaling; Thioctic Acid - administration & dosage; Wnt Signaling Pathway
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.24947

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 H2O2‐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 H2O2‐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. J. Cell. Physiol. 230: 2184–2201, 2015. © 2015 Wiley Periodicals, Inc.