title: Role of fibrillar structure of collagenous carrier in bone sialoprotein-mediated matrix mineralization and osteoblast differentiation.
abstract: To investigate the effects of the microstructure of collagenous carriers on the in vivo function of bone sialoprotein (BSP) in mineralization and osteoblast differentiation, we examined the ultrastructure of reconstituted type I collagen (collagen) and heat-denatured collagen (gelatin) and the in vivo responses to purified bone-derived BSP that was implanted with collagen or gelatin into surgically created 8-mm rat calvarial bone defects. Scanning and transmission electron microscopies revealed that the collagen displayed a fine fibrillar structure with interconnecting spaces between the fibrils/fibers, while the gelatin completely lost this unique three-dimensional structure after denaturation. The rates of in vivo release of BSP from the collagen scaffold were significantly lower than those from the gelatin. Collagen-BSP, but not gelatin-BSP, induced early mineral deposition in the matrix of proliferating repair cells in the calvarial defects at approximately 4-7 days after implantation. Expression levels of osteoblast markers, alkaline phosphatase activity and amounts of new bone synthesized in the collagen-BSP treated defects were significantly greater than that in the gelatin-BSP treated defects (p<0.001). The data suggest that the fibrillar microstructure of reconstituted collagen is essential for retaining BSP at a higher concentration within the defects, which enhances BSP-mediated matrix mineralization and osteoblast differentiation during the repair of rat calvarial defects.
authors.affiliation: Orthopedic Research Laboratory, Department of Orthopedic Surgery, Harvard Medical School and Children's Hospital, Boston, MA 02115, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Xu
authors.forename: Andy L
authors.initials: AL
authors.lastname: Anderson
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Lu
authors.forename: Jinxi
authors.initials: J
authors.lastname: Wang
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001857:Bone Matrix / Q000166:cytology* / Q000378:metabolism*; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D005780:Gelatin / Q000378:metabolism / Q000648:ultrastructure; D058574:Integrin-Binding Sialoprotein; D008855:Microscopy, Electron, Scanning; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000596:Amino Acids; C546873:Ibsp protein, rat; D058574:Integrin-Binding Sialoprotein; D012795:Sialoglycoproteins; D005780:Gelatin; D003094:Collagen