Mesenchymal stem cells (MSCs) promote functional recoveries in pathological experimental models of central nervous system (CNS) and are currently being tested in clinical trials for neurological disorders, but preventive mechanisms of placenta-derived MSCs (PD-MSCs) for Alzheimer's disease are poorly understood. Herein, we investigated the inhibitory effect of PD-MSCs on neuronal cell death and memory impairment in Aβ1–42-infused mice. After intracerebroventrical (ICV) infusion of Aβ1–42 for 14 days, the cognitive function was assessed by the Morris water maze test and passive avoidance test. Our results showed that the transplantation of PD-MSCs into Aβ1–42-infused mice significantly improved cognitive impairment, and behavioral changes attenuated the expression of APP, BACE1, and Aβ, as well as the activity of β-secretase and γ-secretase. In addition, the activation of glia cells and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited by the transplantation of PD-MSCs. Furthermore, we also found that PD-MSCs downregulated the release of inflammatory cytokines as well as prevented neuronal cell death and promoted neuronal cell differentiation from neuronal progenitor cells in Aβ1–42-infused mice. These data indicate that PD-MSC mediates neuroprotection by regulating neuronal death, neurogenesis, glia cell activation in hippocampus, and altering cytokine expression, suggesting a close link between the therapeutic effects of MSCs and the damaged CNS in Alzheimer's disease.

Dalbergia odorifera has been traditionally used as a medicine to treat many diseases. However, the role of 2,4,5-trimethoxyldalbergiquinol (TMDQ) isolated and extracted from D. odorifera in osteoblast function and the underlying molecular mechanisms remain poorly understood. The aim of this study was to investigate the effects and possible underlying mechanisms of TMDQ on osteoblastic differentiation of primary cultures of mouse osteoblasts as an in vitro assay system. TMDQ stimulated osteoblastic differentiation, as assessed by the alkaline phosphatase (ALP) activity, ALP staining, mineralized nodule formation, and the levels of mRNAs encoding the bone differentiation markers, including ALP, bone sialoprotein (BSP), osteopontin, and osteocalcin. TMDQ upregulated the expression of Bmp2 and Bmp4 genes, and increased the protein level of phospho-Smad1/5/8. Furthermore, TMDQ treatment showed the increased mRNA expression of Wnt ligands, phosphorylation of GSK3, and the expression of β-catenin protein. The TMDQ-induced osteogenic effects were abolished by Wnt inhibitor, Dickkopf-1 (DKK1), and bone morphogenetic protein (BMP) antagonist, noggin. TMDQ-induced runt-related transcription factor 2 (Runx2) expression was attenuatted by noggin and DKK1. These data suggest that TMDQ acts through the activation of BMP, Wnt/β-catenin, and Runx2 signaling to promote osteoblast differentiation, and we demonstrate that TMDQ could be a potential agent for the treatment of bone loss-associated diseases such as osteoporosis.

Presenilins are the enzymatic components of γ-secretase complex that cleaves amyloid precursor protein, Notch and β-catenin, which has critical roles in the development of Alzheimer's disease and cancer cell growth. Therefore, in the present study, we studied the effects and mechanisms of PS2 knockout on lung cancer development and possible mechanisms as a key regulator of lung tumor development. We compared carcinogen-induced tumor growth between PS2 knockout mice and wild-type mice. PS2 knockout mice showed increased urethane (1 mg/g)-induced lung tumor incidence when compared with that of wild-type mice with decreased activity of γ-secretase in the lung tumor tissues. Consequently, iPLA2 activities in lung tumor tissues of PS2 knockout mice were much higher than in tumor tissues of wild-type mice. Furthermore, knockdown of PS2 using PS2 siRNA decreased γ-secretase activity with increased iPLA2 activity in the lung cancer cells (A549 and NCI-H460), leading to increased lung cancer cell growth. PS2 knockout mice and PS2 knockdown lung cancer cells showed increased DNA-binding activities of nuclear factor kappa-beta, signal transducer and activator of transcription 3 (STAT3) and AP-1 which are critical transcriptional factors of iPLA2 than those of PS2 wild-type mice and control lung cancer cells. Taken together, these results suggest that the loss of PS2 could have a critical role in lung tumor development through the upregulation of iPLA2 activity by reducing γ-secretase.