Induction of collagen mineralization by a bone sialoprotein--decorin chimeric protein.
The observation that hydroxyapatite (HA) formation from metastable solutions can be induced by nucleating proteins such as bone sialoprotein (BSP) suggests a possible treatment for bone defects. The introduction of a mixture of nucleating protein and type I collagen should result in a defect becoming filled with a mineralized collagenous matrix that is biologically and mechanically compatible and capable of being remodeled. To create a nucleating protein that would interact with collagen fibrils, we combined the putative collagen-binding site of mouse decorin with one of two putative HA-nucleating sites of pig BSP. The resulting chimeric protein induced the formation of HA crystals in a steady-state agarose gel system and bound with high affinity to fibrillar type I collagen. The addition of chimeric protein to collagen gels perfused with low concentrations of calcium and phosphate resulted in the deposition of large, apparently needle-shaped HA crystals on the surface of collagen fibrils. These findings suggest that the BSP-decorin chimeric protein could be capable of inducing the mineralization of collagen in vivo.
Hunter
G K
GK
School of Dentistry, University of Western Ontario, London, Ontario, N6A 5C1, Canada. gkhunter@julian.uwo.ca
Poitras
M S
MS
Underhill
T M
TM
Grynpas
M D
MD
Goldberg
H A
HA
D000818:Animals; D016723:Bone Remodeling; D003094:Collagen / Q000737:chemistry; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006801:Humans; D006882:Hydroxyapatites; D011485:Protein Binding; D011509:Proteoglycans / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012795:Sialoglycoproteins / Q000737:chemistry
C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006882:Hydroxyapatites; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; D003094:Collagen