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Background and Purpose Experimental Approach Key Results Conclusion and Implications Insulin and exenatide are two hypoglycaemic agents that exhibit different osteogenic effects. This study compared the differences between exenatide and insulin in osseointegration in a rat model of Type 2 diabetes (T2D) and explored the mechanisms promoting osteogenesis in this model of T2D.In vivo, micro‐CT was used to detect differences in the peri‐implant bone microstructure in vivo. Histology, dual‐fluorescent labelling, immunofluorescence and immunohistochemistry were used to detect differences in tissue, cell and protein expression around the implants. In vitro, RT‐PCR and western blotting were used to measure the expression of osteogenesis‐ and Wnt signalling‐related genes and proteins in bone marrow mesenchymal stromal cells (BMSCs) from rats with T2D (TBMSCs) after PBS, insulin and exenatide treatment. RT‐PCR was used to detect the expression of Wnt bypass cascade reactions under Wnt inactivation.Micro‐CT and section staining showed exenatide extensively promoted peri‐implant osseointegration. Both in vivo and in vitro experiments showed exenatide substantially increased the expression of osteogenesis‐related and activated the LRP5/6/GSK‐3β/β‐catenin‐related Wnt pathway. Furthermore, exenatide suppressed expression of Bmpr1a to inhibit lipogenesis and promoted expression of Btrc to suppress inflammation.Compared to insulin, exenatide significantly improved osteogenesis in T2D rats and TBMSCs. In addition to its dependence on LRP5/6/GSK‐3β/β‐catenin signalling for osteogenic differentiation, exenatide‐mediated osteomodulation also involves inhibition of inflammation and adipogenesis by BMPR1A and β‐TrCP, respectively. [ABSTRACT FROM AUTHOR]

Background and Purpose: Psoriasis is a chronic immune‐mediated inflammatory skin disease that easily recurs and is difficult to cure. DGT is a novel synthetic heterocyclic diterpenoid, whose structure has not been previously reported. We have investigated the action of DGT against psoriasis, specifically the hyperproliferation of epidermal keratinocytes, angiogenesis and pathogenic inflammatory responses. Experimental Approach We investigated its pharmacokinetics in skin after topical administration. We characterized its pharmacological actions in vitro and in vivo using cell proliferation assay, cell apoptosis assay, diethylstilbestrol‐induced mouse vaginal epithelial cell mitosis model, tube formation assay, cell migration assay, chick embryonic chorioallantoic membrane (CAM) assay, histological, flow cytometric analysis and imiquimod (IMQ)‐induced psoriasis‐like model. Key Results: DGT was found to be mainly distributed in the epidermis and dermis, which indicated that DGT was suitable as a topical treatment. DGT inhibited cell proliferation and induced apoptotic cell death of keratinocytes in vitro and in vivo. Moreover, DGT inhibited endothelial cell proliferation, tube formation and migration of in vitro angiogenesis, as well as in vivo CAM angiogenesis. In an IMQ‐induced psoriasis‐like skin inflammation murine model, topical application of DGT ameliorated keratinocyte proliferation and inflammatory response, especially in IL‐17‐related psoriasiform dermatitis. Furthermore, our results demonstrated that DGT prevented these pathological processes of psoriasis through suppression of STAT3 phosphorylation. Conclusion and Implications: DGT has great potential as a novel therapeutic agent for the treatment of psoriatic skin disease. [ABSTRACT FROM AUTHOR]