title: Zinc in calcium phosphate mediates bone induction: in vitro and in vivo model.
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.
authors.affiliation: Xpand Biotechnology BV, Prof. Bronkhorstlaan 10, Bld 48, 3723 MB Bilthoven, The Netherlands.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Luo
authors.forename: Davide
authors.initials: D
authors.lastname: Barbieri
authors.forename: Noel
authors.initials: N
authors.lastname: Davison
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Yan
authors.forename: Joost D
authors.initials: JD
authors.lastname: de Bruijn
authors.forename: Huipin
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002130:Calcium Phosphates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004285:Dogs; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007477:Ions; D007527:Isoenzymes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D051379:Mice; D008954:Models, Biological; D010012:Osteogenesis / Q000187:drug effects*; D010969:Plastics / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D014961:X-Ray Diffraction; D015032:Zinc / Q000494:pharmacology*
chemical_list: D002130:Calcium Phosphates; D007477:Ions; D007527:Isoenzymes; D010969:Plastics; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D015032:Zinc; C018392:tricalcium phosphate
keywords: Calcium phosphate; Macrophage; Osteogenesis; Stem cell; Zinc