title: A bone substitute with high affinity for vitamin D-binding protein--relationship with niche of osteoclasts.
abstract: The biological activity of osteoblasts and osteoclasts is regulated not only by hormones but also by local growth factors, which are expressed in neighbouring cells or included in bone matrix. Previously, we developed hydroxyapatite (HA) composed of rod-shaped particles using applied hydrothermal methods (HHA), and it revealed mild biodegradability and potent osteoclast homing activity. Here, we compared serum proteins adsorbed to HHA with those adsorbed to conventional HA composed of globular-shaped particles (CHA). The two ceramics adsorbed serum albumin and γ-globulin to similar extents, but affinity for γ-globulin was much greater than that to serum albumin. The chemotactic activity for macrophages of serum proteins adsorbed to HHA was significantly higher than that of serum proteins adsorbed to CHA. Quantitative proteomic analysis of adsorbed serum proteins revealed preferential binding of vitamin D-binding protein (DBP) and complements C3 and C4B with HHA. When implanted with the femur of 8-week-old rats, HHA contained significantly larger amount of DBP than CHA. The biological activity of DBP was analysed and it was found that the chemotactic activity for macrophages was weak. However, DBP-macrophage activating factor, which is generated by the digestion of sugar chains of DBP, stimulated osteoclastogenesis. These results confirm that the microstructure of hydroxyapatite largely affects the affinity for serum proteins, and suggest that DBP preferentially adsorbed to HA composed of rod-shaped particles influences its potent osteoclast homing activity and local bone metabolism.
authors.affiliation: Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ikeda
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Kasai
authors.forename: Eri
authors.initials: E
authors.lastname: Tatsukawa
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kamitakahara
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shibata
authors.forename: Taishi
authors.initials: T
authors.lastname: Yokoi
authors.forename: Takayuki K
authors.initials: TK
authors.lastname: Nemoto
authors.forename: Koji
authors.initials: K
authors.lastname: Ioku
mesh_terms: D000327:Adsorption; D000818:Animals; D001861:Bone Regeneration; D018786:Bone Substitutes / Q000737:chemistry*; D002454:Cell Differentiation; D002516:Ceramics / Q000737:chemistry; D002633:Chemotaxis; D017886:Durapatite / Q000737:chemistry; D005260:Female; D055767:Immobilized Proteins / Q000737:chemistry; D020007:Implants, Experimental; D008264:Macrophages / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry; D014809:Vitamin D-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D014961:X-Ray Diffraction; D005719:gamma-Globulins / Q000737:chemistry
chemical_list: D018786:Bone Substitutes; D055767:Immobilized Proteins; D012709:Serum Albumin; D014809:Vitamin D-Binding Protein; D005719:gamma-Globulins; D017886:Durapatite
keywords: hydroxyapatite; macrophage activating factor; osteoclast; serum proteins; vitamin D-binding protein