Aucubin exerts anti-osteoporotic effects by promoting osteoblast differentiation

Abstract

Osteoporosis is a metabolic disease characterized by reduced osteoblast differentiation and proliferation. Oxidative stress plays a role in the pathogenesis of osteoporosis. Aucubin (AU), an iridoid glycoside, was previously shown to promote osteoblast differentiation. We investigated the effects of AU on MG63 human osteoblast-like cells treated with dexamethasone (Dex) or hydrogen peroxide (H 2 O 2) to induce oxidative damage. AU protected MG63 cells against apoptosis, and promoted increased expression of cytokines associated with osteoblast differentiation, including collagen I, osteocalcin (OCN), osteopontin (OPN), and osterix. In Dex-and H 2 O 2-treated MG63 cells, AU also enhanced the expression of anti-oxidative stressassociated factors in the nuclear respiratory factor 2 signaling pathway, including superoxide dismutases 1 and 2, heme oxygenases 1 and 2, and catalase. In vivo, using a Dex-induced mouse model of osteoporosis, AU promoted increased cortical bone thickness, increased bone density, and tighter trabecular bone. Additionally, it stimulated an increase in the expression of collagen I, OCN, OPN, osterix, and phosphorylated Akt and Smads in bone tissue. Finally, AU stimulated the expression of cytokines associated with osteoblast differentiation in bone tissue and serum. Our data indicate AU may have therapeutic efficacy in osteoporosis.

Proanthocyanidins-Mediated Nrf2 Activation Ameliorates Glucocorticoid-Induced Oxidative Stress and Mitochondrial Dysfunction in Osteoblasts

“…The osteogenic function of osteoblasts is inhibited by oxidative stress and mitochondrial dysfunction [ 4 , 5 ]. Therefore, we next assessed the effect of PAC on the early differentiation and mineralization of the Dex-treated cells.…”

“…Studies show that it can inhibit osteoblast proliferation and promote apoptosis [ 31 , 32 ] by triggering oxidative stress and mitochondrial dysfunction. Li et al found that Dex treatment increased intracellular ROS accumulation as well as the dissipation of MMP in MG63 cells [ 4 ]. The mitochondrial accumulation of ROS induced a vicious cycle of oxidative stress and mitochondrial dysfunction, which culminated in the activation of the apoptotic pathway [ 33 ].…”

“…The major cause of bone loss in GIOP is the decrease in the osteoblast function. Dex inhibited osteoblast differentiation and accelerated the development of bone loss [ 4 ]. In addition, Dex disharmonizes organelle homeostasis within osteoblasts, thereby exacerbating its destiny of malfunction [ 32 ].…”

“…After one week of acclimatization, the rats were randomly divided into the vehicle control (sham group), untreated GIOP, and PAC-treated GIOP groups ( n = 15 each). GIOP was induced by daily intraperitoneal injections of 5 mg/kg Dex for 4 weeks as previously described [ 4 ], and the rats in the sham group received daily injections of PBS during the same period. After 4 weeks of Dex treatment, the animals showing signs of osteoporosis as per X-ray radiograph imaging were treated with the vehicle or PAC (10 mg/kg) for another 8 weeks.…”

Black and Green Tea as Well as Specialty Teas Increase Osteoblast Mineralization with Varying Effectiveness

“…[32][33][34] Several studies have also demonstrated that antioxidants from plant sources, such as apigenin, curcumin, and aucubin, are able to increase osteoblast viability in many osteoblast cell models, including; Saos-2, MC3T3-E1, and MG-63. [35][36][37] These findings provide support that polyphenols found in the tea likely acted as antioxidants to reduce oxidative stress thus increasing activity and mineralization. More specifically, using the same cell model, researchers have observed both elevated cell activity and mineralization in response to tea (black, green, and rooibos).…”