Osteophilic and Dual‐Regulated Alendronate‐Gene Lipoplexes for Reversing Bone Loss

Abstract

The pathogenesis of postmenopausal osteoporosis (PMOP) is mainly determined by the adhesion of osteoclasts to the bone matrix and the involvement of various molecules in bone resorption. The dual regulation strategy of the physical barriers of bone matrix and intracellular gene regulation generated by advanced biomaterials is a decent alternative for the treatment of PMOP. Herein, for the first time, it is identified that hsa‐miR‐378i/mmu‐miR‐378a‐3p are closely associated with PMOP. Then, an osteophilic and dual‐regulated alendronate‐gene lipoplex (antagomir@Aln‐Lipo), composed of medicative alendronate‐functionalized liposomal vehicle and encapsulated specific microRNAs is engineered, for bone‐targeting delivery of genes to achieve combined mitigation of bone loss. Alendronate targets hydroxyapatite in the bone matrix and occupies the adhesion site of osteoclasts, thus providing the “physical barriers”. Antagomir is coupled precisely to specific endogenous microRNAs, thus providing the “genetic signals”. These functionalized lipoplexes exhibited long‐term stability and good transfection efficiency. It is proven that antagomir@Aln‐Lipo could synergistically regulate osteoclastogenesis and bone resorption in vitro and in vivo. Furthermore, intravenous injection of antagomir@Aln‐Lipo efficiently reverses bone loss through a dual mechanism driven by alendronate and antagomir‐378a‐3p. In conclusion, the osteophilic and dual‐regulated antagomir@Aln‐Lipo offers a brand‐new bifunctional strategy for the precise treatment of PMOP.

Vascular endothelial cells-derived exosomes synergize with curcumin to prevent osteoporosis development

“…The osteophilic and dually regulated isotype replacement antibody @ Aln-Lipo provides a bifunctional strategy for precision therapy of PMOP. 30 Through miRNA-seq sequencing, we screened for key factors by which EC-EXOs regulate the fate differentiation of BMSCs. Our study showed that the expression of miR-3p-975_4191 was significantly greater in EC-EXOs than in BMSCs and HMEC-1 cells.…”

MiRNAs Expression Modulates Osteogenesis in Response to Exercise and Nutrition

“…As we already said, the miRNAs are a group of small non-coding RNAs that regulate gene expression at the post-transcriptional level and cellular processes [ 39 , 40 , 41 ]. Notwithstanding most miRNAs are found inside cells, there is a large portion that are release in the body fluids such as blood, urine, saliva, seminal fluid, breast milk and other biological specimens in response to tissue damage, apoptosis and necrosis through active transport into exosomes or bonded to a protein as previously described [ 42 ].…”

Epigenetic Biomarkers Modulate Osteogenesis in Response to Exercise and Nutrition

“…As we already said, the miRNAs are a group of small non-coding RNAs that regulate gene expression at the post-transcriptional level and cellular processes [39][40][41]. Notwithstanding most miRNAs are found inside cells, there is a large portion that are release in the body fluids such as blood, urine, saliva, seminal fluid, breast milk and other biological specimens in response to tissue damage, apoptosis and necrosis through active transport into exosomes or bonded to a protein as previously described [42].…”