Title:Nanoparticles Targeting Delivery Antagomir-483-5p to Bone Marrow
Mesenchymal Stem Cells Treat Osteoporosis by Increasing Bone Formation
Volume: 18
Issue: 1
Author(s): Yue Zhou, Hao Jia, Aihua Hu, Rangru Liu, Xiangzhou Zeng and Hua Wang*
Affiliation:
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine, Hainan
Medical University, Haikou, 571199, China
Keywords:
Osteoporosis treatment, Antagomir-483-5p, BMSC osteoblastic differentiation, MAPK1, Smad5, Targeted drug delivery.
Abstract:
Background: Promoting bone marrow mesenchymal stem cell (BMSC) osteoblastic differentiation
is a promising therapeutic strategy for osteoporosis (OP). The present study demonstrates that miR-
483-5p inhibits the osteogenic differentiation of BMSCs. Therefore, selectively delivering the nanoparticles
carrying antagomir-483-5p (miR-483-5p inhibitor) to BMSCs is expected to become an effective
treatment drug for OP.
Methods: Real-time PCR assays were used to analyze miR-483-5p, ALP and Bglap levels in BMSCs of
ovariectomized and aged osteoporotic mice. Immunoglobulin G and poloxamer-188 encapsulated the
functional small molecules, and a BMSC-targeting aptamer was employed to confirm the direction of the
nanoparticles to selectively and efficiently deliver antagomir-483-5p to BMSCs in vivo. Luciferase assays
were used to determine the target genes of miR-483-5p. Western blot assays and immunohistochemistry
staining were used to detect the targets in vitro and in vivo.
Results: miR-483-5p levels were increased in BMSCs of ovariectomized and aged osteoporotic mice.
Inhibiting miR-483-5p levels in BMSCs by antagomir-483-5p in vitro promoted the expression of bone
formation markers, such as ALP and Bglap. The FAM-BMSC-aptamer-nanoparticles carrying antagomir-
483-5p were taken up by BMSCs, resulting in stimulation of BMSC osteoblastic differentiation in vitro
and osteoporosis prevention in vivo. Furthermore, our research demonstrated that mitogen-activated protein
kinase 1 (MAPK1) and SMAD family member 5 (Smad5) were direct targets of miR-483-5p in regulating
BMSC osteoblastic differentiation and osteoporosis pathological processes.
Conclusions: The important therapeutic role of FAM-BMSC-aptamer-nanoparticles carrying antagomir-
483-5p in osteoporosis was established in our study. These nanoparticles are a novel candidate for the
clinical prevention and treatment of osteoporosis. The optimized, targeted drug delivery platform for
small molecules will provide new ideas for treating clinical diseases.
