[Show abstract][Hide abstract] ABSTRACT: Gold nanoparticles (AuNPs) have shown great promise for a variety of applications, including chemistry, biology, and medicine. Recently, AuNPs have found promising applications in cartilage and bone repair. However, to realize the above promised applications, more work needs to be carried out to clarify the interactions between biological systems and AuNPs. In the present study, primary osteoblasts were used to evaluate the biocompatibility of 20-nm and 40-nm AuNPs, including morphology, proliferation, differentiation, gene and protein expression, and the underlying mechanisms. The results demonstrated that AuNPs were taken up by osteoblasts and aggregated in perinuclear compartment and vescular structures, but no morphological changes were observed. AuNPs could significantly promote the proliferation of osteoblasts, enhance the ALP activities, and increase the number of bone nodules and calcium content in vitro. In addition, the expression of BMP-2, Runx-2, OCN and Col-1 was remarkably up-regulated in the presence of AuNPs. It is noteworthy that 20-nm AuNPs are more potent than 40-nm AuNPs in regulating osteoblast activities. Besides, AuNPs increased the level of ERK phosphorylation/total ERK, suggesting the activation of ERK/MAPK pathway is involved in above activities. In conclusion, AuNPs exhibited great biocompatibility with osteoblasts, and have tremendous potential to be used as drug and/or gene delivery carrier for bone and tissue engineering in the future.
Materials Science and Engineering C 09/2014; 42:70–77. DOI:10.1016/j.msec.2014.04.042 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidences suggest that Herba epimedii has the potential benefits against osteoporosis. However, previous studies were focused on the crude extract, total flavonoids (TF) and icariin (ICA), and the detailed molecular mechanisms of action and structure-activity relationship (SAR) remain unclear. Herein we aimed to systematically investigate the effects of Herba epimedii flavonoids (HEF) on the activity of osteoclasts, and explore the potential SAR. Both ICA and baohuoside-1 (BS) significantly inhibited the proliferation of RAW 264.7 cells (IC(50) 25 μM and 67 μM, respectively). Treatment of ICA resulted in G2/M arrest and apoptosis in RAW 264.7 cells as early as 12 h. Besides, HEF remarkably suppressed vitamin D-induced differentiation of osteoclasts in rabbit bone marrow cells and the bone resorption of rabbit mature osteoclasts in vitro. It is notable that the inhibitory effect of 100 μM ICA and BS on osteoclast formation is almost 90%; and the inhibition rate on bone resorption is 50% and 80%, respectively. Besides, RANKL-induced osteoclast formation from RAW 264.7 cells and the expression of TRAP, CA II, CTSK and MMP-9 was significantly reduced by the treatment of 25 μM HEF and 17β-estradiol (ES), and the inhibitory strength increases in the order TF < ES < ICA < BS, which was blocked by ICI182780 suggesting that the regulation of osteoclast activity might be ER dependent. Furthermore, the free hydroxyl group at C-7 of BS played an important role in the SAR for anti-osteoclast action. To conclude, HEF could regulate the formation and activity of osteoclasts by inhibiting the proliferation and differentiation, inducing apoptosis and cell cycle arrest and suppressing bone resorption of osteoclasts. Changes in osteoclast activity are probably mediated predominantly by interaction with nuclear estrogen receptors and via mitochondrial pathway. HEF, especially BS, has great potential for the prevention and treatment of osteoporosis.
[Show abstract][Hide abstract] ABSTRACT: The adipogenic capacity of mesenchymal stem cells (MSCs) and the involvement of beta-adrenergic signals in lipolysis and thermogenesis have been well established. However, little is known about the development of beta-adrenergic receptor (beta-AR) systems and the role of beta-adrenergic signals in adipogenic differentiation of MSCs. In this study, we demonstrated that both the mRNA and protein levels of beta2- and beta3-AR were up-regulated following adipogenesis of mouse bone marrow derived MSCs. We also established that beta-AR agonists negatively while antagonists positively affected MSC adipogenesis. Both the beta2- and beta3-AR were involved in MSC adipogenesis, with beta3-AR being the predominant subtype. The effect of beta-ARs on MSC adipogenesis was at least partly mediated via the cAMP/PKA signaling pathway. These findings suggested that MSC is also a target for beta-adrenergic regulation, and beta-adrenergic signaling (major beta3-signaling) plays a role in MSC adipogenesis.
[Show abstract][Hide abstract] ABSTRACT: The osteogenic capacity of mesenchymal stem cells (MSCs) and the importance of beta-adrenergic signals in bone formation and resorption have been well investigated. However, little is known about the development of beta-adrenergic receptor (beta-AR) systems and the role of beta-adrenergic signals in osteogenic differentiation of MSCs, which is critically important in bone physiology and pharmacology. In this study, we demonstrated that both the mRNA and protein levels of beta2- and beta3-AR are up-regulated following osteogenesis of mouse MSCs. We also established that beta-AR agonists negatively while antagonists positively affect MSC osteogenesis. Both beta2- and beta3-AR are involved in MSC osteogenesis, with beta2-AR being dominant. The effect of beta-ARs on MSC osteogenesis is partly mediated via the cAMP/PKA signaling. These findings suggest that MSC is also a target for beta-adrenergic regulation and beta-adrenergic signaling plays a role in MSC osteogenesis.
Archives of Biochemistry and Biophysics 02/2010; 496(2):77-83. DOI:10.1016/j.abb.2010.01.016 · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We extracted and isolated three natural styryl lactones from Goniothalamus griffithii Hook f. Thoms and investigated their cytotoxicity on a panel of three hepatocyte cell lines, HepG2, drug resistant HepG2 (HepG2-R) and primary cultured normal mice hepatocyte in order to find candidates of potential anti-cancer drugs which have low toxicity on normal cells and high effect on tumors or drug resistant tumors. All the three styryl lactones showed evident cytotoxic activities on both HepG2 and HepG2-R cell lines; however, gonithalamin and goniodiol shows less toxicity on normal mice hepatocyte as the IC(50) values of them on normal mice hepatocyte were about three times of that on HepG2. Morphological observation and cell cycle analysis were employed to elucidate the mechanisms of cytotoxicity of the tested compounds. Many apoptotic cells were observed in gonithalamin- and altholactone-treated cells, whereas, cells with chromosomes gathered at the equator were easily found in goniodiol-treated cultures. The analysis of cell cycle showed that G(2)/M arrest contributed to goniothalimin- and gonidiol-caused cell death and apoptosis was the cause of gonithalamin- and altholactone-induced cell death. Our results suggest that the three styryl lactones may be prospectively developed into anti-tumor drugs, especially on treating drug-resistance tumor after structure modification.