한빛사논문
Seoyeon Kim 1 †, Haein Lee 1 †, Jiyeon Hong 1, Seung Hyun L Kim 2, Euntaek Kwon 2, Tai Hyun Park 1 2 3 4 *, Nathaniel S Hwang 1 2 3 *
1School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
2Interdisciplinary Program in Bioengineering, Seoul National University, 1 Gwanak-ro, Gwanak gu, Seoul, 08826, Republic of Korea.
3BioMAX/N-Bio Institute, Institute of BioEngineerig, Seoul National University, 1 Gwanakro, Gwanak-gu, Seoul, 08826, Republic of Korea.
4Department of Nutritional Science and Food Management, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Republic of Korea.
†S.K. and H.L. contributed equally to this work.
*Corresponding author: correspondence to Tai Hyun Park or Nathaniel S Hwang
Abstract
The onset of osteoporosis leads to a gradual decrease in bone density due to an imbalance between bone formation and resorption. To achieve optimal drug efficacy with minimal side effects, targeted drug delivery to the bone is necessary. Previous studies have utilized peptides that bind to hydroxyapatite, a mineral component of bone, for bone-targeted drug delivery. In this study, a hydroxyapatite binding (HAB) tag is fused to 30Kc19α-Runt-related transcription factor 2 (RUNX2) for bone-targeting. This recombinant protein can penetrate the nucleus of human mesenchymal stem cells (hMSCs) and act as a master transcription factor for osteogenesis. The HAB tag increases the binding affinity of 30Kc19α-RUNX2 to mineral deposition in mature osteoblasts and bone tissue, without affecting its osteogenic induction capability. In the osteoporosis mouse model, intravenous injection of HAB-30Kc19α-RUNX2 results in preferential accumulation in the femur and promotes bone formation while reducing toxicity in the spleen. These findings suggest that HAB-30Kc19α-RUNX2 may be a promising candidate for bone-targeted therapy in osteoporosis.
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