Downregulation of GNAS inhibits osteogenesis of bone marrow mesenchymal stem cells and promotes osteoporosis through the Wnt pathway.

OBJECTIVE: This study aims to explore the role of GNAS in accelerating the progression of osteoporosis by inhibiting osteogenesis of BMSCs by the Wnt pathway. PATIENTS AND METHODS: GNAS levels in OP tissues and BMSCs undergoing osteogenesis for different time points were detected. Regulatory effects of GNAS on osteogenesis-related gene expressions, ALP activity, capability of mineralization, and activation of the Wnt pathway in BMSCs were assessed through a series of functional experiments. At last, rescue experiments were performed to further verify the significance of the Wnt pathway during GNAS-mediated osteogenesis development. RESULTS: GNAS was downregulated in OP tissues relative to normal bone tissues. With the prolongation of osteogenesis, GNAS level gradually increased in BMSCs. Knockdown of GNAS downregulated expression levels of ALP and RUNX2, and attenuated ALP activity and capability of mineralization in BMSCs. GNAS was able to activate the Wnt pathway in BMSCs. Notably, overexpression of Wnt3a could reverse the regulatory effects of GNAS on osteogenesis-related gene expressions, ALP activity, and capability of mineralization in BMSCs. CONCLUSIONS: Downregulation of GNAS suppresses osteogenesis of BMSCs through the Wnt pathway, thus aggravating the progression of osteoporosis.

2Hz-electroacupuncture attenuates heroin-seeking behaviors via adjusts CB1-Rs and CB2-Rs expression in relapse-relevant brain regions of heroin self-administration rats.

Opiate addiction has a high rate of relapse. The accumulating evidence shows that electroacupuncture (EA) may be effective for the treatment of opiate relapse. However, the change of expression of CB1-Rs and CB2-Rs involve in 2Hz EA anti-relapse pathway is still unclear. To explore the changes of expression of CB1-Rs and CB2-Rs, heroin self-administration (SA) model rats were adopted and treated using 2Hz EA. The expressions of CB1-Rs and CB2-Rs were observed using immunohistochemistry method. The results showed that, compared with the control group, active pokes in the heroin-addicted group increased, while the active pokes decreased significantly in 2Hz EA group compared with heroin-addicted group. Correspondingly, the expression of CB1-Rs in prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) all increased significantly while the expression of CB2-Rs in those relapse-relevant brain regions decreased obviously in heroin-addicted group when compared with the control group. In addition, the expression of CB1-Rs obviously decreased in the 2Hz EA group while the expression of CB2-Rs in those relapse-relevant brain regions increased significantly when compared with the heroin-addicted group. It indicated that 2Hz EA could attenuate the heroin-evoked seeking behaviors effectively. The anti-relapse effects of 2Hz EA might be related to the decrease of CB1-Rs and increase of CB2-Rs expression in relapse-relevant brain regions of heroin SA rats.