title: Multifunctional role of osteopontin in directing intrafibrillar mineralization of collagen and activation of osteoclasts.
abstract: Mineralized collagen composites are of interest because they have the potential to provide a bone-like scaffold that stimulates the natural processes of resorption and remodeling. Working towards this goal, our group has previously shown that the nanostructure of bone can be reproduced using a polymer-induced liquid-precursor (PILP) process, which enables intrafibrillar mineralization of collagen with hydroxyapatite to be achieved. This prior work used polyaspartic acid (pASP), a simple mimic for acidic non-collagenous proteins, to generate nanodroplets/nanoparticles of an amorphous mineral precursor which can infiltrate the interstices of type-I collagen fibrils. In this study we show that osteopontin (OPN) can similarly serve as a process-directing agent for the intrafibrillar mineralization of collagen, even though OPN is generally considered a mineralization inhibitor. We also found that inclusion of OPN in the mineralization process promotes the interaction of mouse marrow-derived osteoclasts with PILP-remineralized bone that was previously demineralized, as measured by actin ring formation. While osteoclast activation occurred when pASP was used as the process-directing agent, using OPN resulted in a dramatic effect on osteoclast activation, presumably because of the inherent arginine-glycine-aspartate acid ligands of OPN. By capitalizing on the multifunctionality of OPN, these studies may lead the way to producing biomimetic bone substitutes with the capability of tailorable bioresorption rates.
authors.affiliation: Department of Materials Science & Engineering, University of Florida, Gainesville, FL 32611-6400, USA.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Rodriguez
authors.forename: Taili
authors.initials: T
authors.lastname: Thula-Mata
authors.forename: Edgardo J
authors.initials: EJ
authors.lastname: Toro
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Yeh
authors.forename: Carl
authors.initials: C
authors.lastname: Holt
authors.forename: L Shannon
authors.initials: LS
authors.lastname: Holliday
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Gower
mesh_terms: D000818:Animals; D018775:Bone Demineralization Technique; D001862:Bone Resorption / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002113:Calcification, Physiologic; D002417:Cattle; D024022:Fibrillar Collagens / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008903:Minerals / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D053495:Osteopontin / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D024022:Fibrillar Collagens; D008903:Minerals; D011108:Polymers; D053495:Osteopontin
keywords: Biomineralization; Bioresorption; Bone graft; Osteoclast; Osteopontin