A novel biologically hierarchical hydrogel with osteoblast precursor‐targeting extracellular vesicles ameliorates bone loss in vivo via the sequential action of <scp>antagomiR</scp>‐200b‐3p and <scp>antagomiR</scp>‐130b‐3p

Dai, Hanhao; Yu, Yunlong; Han, Junyong; Luo, Jun; Song, Chao; Deng, Zhibo; Wu, Yijing; Ke, Dianshan; Xu, Jie

doi:10.1111/cpr.13426

Cited by 2 publications

(1 citation statement)

References 71 publications

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“…[ 11 ] Antagomir is a special chemically engineered miRNA antagonist, which has good stability and could specifically silence endogenous miRNAs in animals. [ 12 ] Accordingly, functional miRNAs can be discovered based on preosteoclasts or osteoclasts, and specially designed antagomir can successfully control the expression of target genes, which is anticipated to be an effective strategy for managing osteoporosis.…”

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confidence: 99%

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

Zhang

et al. 2023

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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.

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Section: Introductionmentioning

confidence: 99%

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

Zhang

et al. 2023

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A novel biologically hierarchical hydrogel with osteoblast precursor‐targeting extracellular vesicles ameliorates bone loss in vivo via the sequential action of antagomiR‐200b‐3p and antagomiR‐130b‐3p

Dai

Han

et al. 2023

Cell Proliferation

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Osteoporotic fracture is a major health problem plaguing the ageing society, and improving its treatment is an urgent challenge. How to ameliorate bone loss determines the recovery of such fractures. Extracellular vesicle (EV)‐loaded hydrogel has the capacity to treat osteoporotic fractures due to its pro‐osteogenic property. And balancing proliferation and maturation of osteoblast precursors (OBPs) is of great significance to avoid OBP depletion, which is lacking in current treatment. Based on osteoblastogenic miRNAs, this study aimed to explore the efficacies of the combination of hierarchical hydrogel and EVs altering functional miRNAs level in bone loss. Through bioinformatics analyses, we screened out proliferative gene‐targeting miR‐200b‐3p and osteogenic gene‐targeting miR‐130b‐3p. And antagomiR‐200b‐3p (ant‐200b) enhanced OBP proliferation, and antagomiR‐130b‐3p (ant‐130b) promoted OBP differentiation. After confirming the directional effect of Fibronectin (Fn1) on OBPs, we prepared OBP‐targeting EVs. Furthermore, encapsulation of two antagomiRNAs in EVs enhanced the respective effect of ant‐200b and ant‐130b. Notably, hierarchically injectable hydrogel exerted an effective function in promoting the sequential delivery of EVs‐200b and EVs‐130b. Importantly, hierarchical hydrogel containing dual EVs effectively ameliorated bone loss. Overall, hierarchical hydrogel based on two antagomiRNAs effectively improves bone loss in vivo due to its role in promoting OBP proliferation and maturation sequentially.

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A novel biologically hierarchical hydrogel with osteoblast precursor‐targeting extracellular vesicles ameliorates bone loss in vivo via the sequential action of antagomiR‐200b‐3p and antagomiR‐130b‐3p

Cited by 2 publications

References 71 publications

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

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

A novel biologically hierarchical hydrogel with osteoblast precursor‐targeting extracellular vesicles ameliorates bone loss in vivo via the sequential action of antagomiR‐200b‐3p and antagomiR‐130b‐3p

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