In this review the authors outline traditional antiresorptive pharmaceuticals, such as bisphosphonates, monoclonal antibodies against RANKL, SERMs, as well as a drug with an anabolic effect on the skeleton, parathormone. However, there is also a focus on non-traditional strategies used in therapy for osteolytic diseases. The newest antiosteoporotic pharmaceuticals increase osteoblast differentiation via BMP signaling (harmine), or stimulate osteogenic differentiation of mesenchymal stem cells through Wnt/β-catenin (icarrin, isoflavonoid caviunin, or sulfasalazine). A certain promise in the treatment of osteoporosis is shown by molecules targeting non-coding microRNAs (which are critical for osteoclastogenesis) or those stimulating osteoblast activity via epigenetic mechanisms. Vitamin D metabolites have specific antiosteoporotic potencies, modulating the skeleton not only via mineralization, but markedly also through the direct effects on the bone microstructure., I. Zofkova, J. Blahos., and Obsahuje bibliografii
Proliferation and migration of retinal endothelial cells (RECs) contribute to the development of diabetic retinopathy. PLAG1 (pleomorphic adenoma gene 1) functions as a zinc-finger transcription factor to participate in the development of lipoblastomas or pleomorphic adenomas of the salivary glands through regulation of cell proliferation and migration. The role of PLAG1 in diabetic retinopathy was investigated in this study. Firstly, RECs were induced under high glucose conditions, which caused reduction in viability and induction of apoptosis in the RECs. Indeed, PLAG1 was elevated in high glucosetreated RECs. Functional assays showed that silence of PLAG1 increased viability and suppressed apoptosis in high glucose-induced RECs, accompanied with up-regulation of Bcl-2 and down-regulation of Bax and cleaved caspase-3. Moreover, migration of RECs was promoted by high glucose conditions, while repressed by knockdown of PLAG1. High glucose also triggered angiogenesis of RECs through up-regulation of vascular endothelial growth factor (VEGF). However, interference of PLAG1 reduced VEGF expression to retard the angiogenesis. Silence of PLAG1 also attenuated high glucose-induced up-regulation of Wnt3a, β-catenin and c-Myc in RECs. Moreover, silence of PLAG1 ameliorated histopathological changes in the retina of STZ-induced diabetic rats through down-regulation of β-catenin. In conclusion, knockdown of PLAG1 suppressed high glucose-induced angiogenesis and migration of RECs, and attenuated diabetic retinopathy by inactivation of Wnt/ β-catenin signalling.
Adjuvant therapy and radiotherapy improves the survival of patients with metastatic and locally advanced gastric cancer (GC). However, the resistance to radiotherapy limits its clinical usage. Rhotekin 2 (RTKN2) functions as an oncogene and confers resistance to ultraviolet B-radiation and apoptosis- inducing agents. Here, the role of RTKN2 in radiosensitivity of GC cell lines was investigated. RTKN2 was found to be elevated in GC tissues and cells. A series of functional assays revealed that overexpression of RTKN2 induced GC cell proliferation, promoted GC cell migration and invasion, while inhibiting GC cell apoptosis. However, silence of RTKN2 promoted GC cell apoptosis, while repressing GC cell proliferation, invasion and migration. GC cells were exposed to irradiation, and data from cell survival and apoptotic assays showed that knock-down of RTKN2 enhanced radiosensitivity of GC through up-regulation of apoptosis and down-regulation of proliferation in irradiation-exposed GC cells. Moreover, the protein expression of β-catenin and c-Myc in GC cells was enhanced by RTKN2 over-expression, but reduced by RTKN2 silence. Interference of RTKN2 down-regulated nuclear β-catenin expression, while up-regulating cytoplasmic β-catenin in GC. In conclusion, RTKN2 contributed to cell growth and radioresistance in GC through activation of Wnt/β-catenin signalling.