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Zinc in calcium phosphate mediates bone induction: In vitro and in vivo model
Institution:1. Dental Clinical Research Center, Dentistry School, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil;2. LABIOMAT, Brazilian Center for Physics Research, CBPF, Rio de Janeiro, Brazil;3. Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;4. Nuclear Instrumentation Laboratory, Nuclear Engineering Program, COPPE, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;5. Bioengineering Division, National Institute of Metrology, Quality and Technology, Duque de Caxias, Rio de Janeiro, Brazil;1. School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China;2. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China;3. College of Pharmacy, Ewha Women''s University, Seoul 03760, Republic of Korea;4. College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA
Abstract:Zinc-containing tricalcium phosphate (Zn-TCP) was synthesized to investigate the role of zinc in osteoblastogenesis, osteoclastogenesis and in vivo bone induction in an ectopic implantation model. Zinc ions were readily released in the culture medium. Zn-TCP with the highest zinc content enhanced the alkaline phosphatase activity of human bone marrow stromal cells and tartrate-resistant acid phosphatase activity, as well as multinuclear giant cell formation of RAW264.7 monocyte/macrophages. RAW264.7 cultured with different dosages of zinc supplements in medium with or without zinc-free TCP showed that zinc could influence both the activity and the formation of multinuclear giant cells. After a 12-week implantation in the paraspinal muscle of canines, de novo bone formation and bone incidence increased with increasing zinc content in Zn-TCP – up to 52% bone in the free space. However, TCP without zinc induced no bone formation. Although the observed bone induction cannot be attributed to zinc release alone, these results indicate that zinc incorporated in TCP can modulate bone metabolism and render TCP osteoinductive, indicating to a novel way to enhance the functionality of this synthetic bone graft material.
Keywords:Zinc  Calcium phosphate  Macrophage  Stem cell  Osteogenesis
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