한빛사 논문
Na-Hyun Leea,b, Min Sil Kanga,b, Tae-Hyun Kima,b, Dong Suk Yoona,b, Nandin Mandakhbayara,b, Seung Bin Joa, Hye Sung Kima,e,f,g,h, Jonathan C. Knowlesb,c,d,g, Jung-Hwan Leea,b,e,f,g,h,i,*, Hae-Won Kima,b,e,f,g,h,i,*
aInstitute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea
bDepartment of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea
cDivision of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, 256 Grays Inn Road, London, WC1X 8LD, UK
dThe Discoveries Centre for Regenerative and Precision Medicine, UCL Campus, London, UK
eDepartment of Biomaterials Science, School of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea
fDepartment of Regenerative Dental Medicine, School of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea
gCell & Matter Institute, Dankook University, Cheonan, 31116, Republic of Korea
hMechanobiology Dental Medicine Research Center, Cheonan, 31116, Republic of Korea
iUCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea
*Corresponding author
Abstract
Repair of defective hard-tissues in osteoporotic patients faces significantly challenges with limited therapeutic options. Although biomedical cements are considered promising materials for healthy bone repair, their uses for healing osteoporotic fracture are clinically limited. Herein, strontium-releasing-nanoscale cement was introduced to provide dual therapeutic-actions (pro-osteogenesis and anti-osteoclastogenesis), eventually for the regeneration of osteoporotic bone defect. The Sr-nanocement hardened from the Sr-doped nanoscale-glass particles was shown to release multiple ions including silicate, calcium and strontium at doses therapeutically relevant over time. When the Sr-nanocement was treated to pre-osteoblastic cells, the osteogenic mRNA level (Runx2, Opn, Bsp, Ocn), alkaline phosphatase activity, calcium deposition, and target luciferase reporter were stimulated with respect to the case with Sr-free-nanocement. When treated to pre-osteoclastic cells, the Sr-nanocement substantially reduced the osteoclastogenesis, such as osteoclastic mRNA level (Casr, Nfatc1, c-fos, Acp, Ctsk, Mmp-9), tartrate-resistant acid trap activity, and bone resorption capacity. In particular, the osteoclastic inhibition resulted in part from the interactive effect of osteoblasts which were activated by the Sr-nanocement, i.e., blockage of RANKL (receptor activator of nuclear factor-κB ligand) binding by enhanced osteoprotegerin and the deactivated Nfatc1. The Sr-nanocement, administered to an ovariectomized tibia defect (osteoporotic model) in rats, exhibited profound bone regenerative potential in cortical and surrounding trabecular area, including increased bone volume and density, enhanced production of osteopromotive proteins, and more populated osteoblasts, together with reduced signs of osteoclastic bone resorption. These results demonstrate that Sr-nanocement, with its dual effects of osteoclastic inhibition and osteogenic-stimulation, can be considered an effective nanotherapeutic implantable biomaterial platform for the treatment of osteoporotic bone defects.
Keywords : Strontium doped nanoglass particles, Osteoporosis treatment, Osteoclastic inhibition, Osteogenic stimulation, Osteoblast-osteoclast interaction
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