Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.
Poly(amidoamine) (PAMAM) dendrimers have been widely used as nucleic acid delivery vectors. To improve the transfection efficacy, ligands such as amino acid, peptide and lipid are conjugated to the periphery of dendrimers. However, the structures of these ligands are generally flexible, and few reports about rigid‐ligand‐modified dendrimers are reported. In this work, three novel PAMAM dendrimers (G5‐1, G5‐2 and G5‐3) modified with rigid naphthalimide were synthesized as nucleic acid delivery vectors. Magnetic resonance spectroscopy showed that the average numbers of naphthalimide molecules conjugated on the PAMAM periphery in compounds G5‐1, G5‐2 and G5‐3 are 8, 30 and 50, respectively. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay revealed good cytocompatibility of these vectors in multiple cell lines, including MG63, HeLa, HEK293 and MC3T3‐E1 cells, with a cell survival rate of more than 90% in most cases. Among the three dendrimers, G5‐1 with fewer naphthalimide molecules showed stronger RNA binding ability than G5‐2 and G5‐3. G5‐1 also exhibited the best gene silencing efficacy at a dendrimer to miRNA weight ratio of 1:2 in MC3T3‐E1 cells, which is much higher than the commercial transfection agent Lipofectamine 2000 tested under the same conditions. In addition, G5‐1 showed high transfection efficacy in plasmid DNA‐mediated luciferase expression experiments. These results suggest that rigid ligand modification can be developed as a new strategy to design safe and highly efficient nucleic acid delivery vectors. © 2021 Society of Industrial Chemistry.
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