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Dual actions of osteoclastic-inhibition and osteogenic-stimulation through strontium-releasing bioactive nanoscale cement imply biomaterial-enabled osteoporosis therapy

Lee, NH; Kang, MS; Kim, TH; Yoon, DS; Mandakhbayar, N; Jo, SB; Kim, HS; ... Kim, HW; + view all (2021) Dual actions of osteoclastic-inhibition and osteogenic-stimulation through strontium-releasing bioactive nanoscale cement imply biomaterial-enabled osteoporosis therapy. Biomaterials , 276 , Article 121025. 10.1016/j.biomaterials.2021.121025. Green open access

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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.

Type: Article
Title: Dual actions of osteoclastic-inhibition and osteogenic-stimulation through strontium-releasing bioactive nanoscale cement imply biomaterial-enabled osteoporosis therapy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.biomaterials.2021.121025
Publisher version: https://doi.org/10.1016/j.biomaterials.2021.121025
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Strontium doped nanoglass particles, Osteoporosis treatment, Osteoclastic inhibition, Osteogenic stimulation, Osteoblast-osteoclast interaction
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute > Biomaterials and Tissue Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10132494
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