title: Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation.
abstract: Several investigations have demonstrated a precise balance to exist between bone morphogenetic protein (BMP) agonists and antagonists, dictating BMP signaling and osteogenesis. We report a novel approach to manipulate BMP activity through a down-regulation of the potent BMP antagonist Noggin, and examined the effects on the bone forming capacity of osteoblasts. Reduction of noggin enhanced BMP signaling and in vitro osteoblast bone formation, as demonstrated by both gene expression profiles and histological staining. The effects of noggin suppression on in vivo bone formation were also investigated using critical-sized calvarial defects in mice repaired with noggin-suppressed osteoblasts. Radiographic and histological analyses revealed significantly more bone regeneration at 2 and 4 weeks post-injury. These findings strongly support the concept of enhanced osteogenesis through a down-regulation in Noggin and suggest a novel approach to clinically accelerate bone formation, potentially allowing for earlier mobilization of patients following skeletal injury or surgical resection.
authors.affiliation: Department of Surgery, Stanford University School of Medicine, Stanford University, Stanford, California 94305, USA.
authors.forename: Derrick C
authors.initials: DC
authors.lastname: Wan
authors.forename: Jason H
authors.initials: JH
authors.lastname: Pomerantz
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Brunet
authors.forename: Jae-Beom
authors.initials: JB
authors.lastname: Kim
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Chou
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Wu
authors.forename: Richard
authors.initials: R
authors.lastname: Harland
authors.forename: Helen M
authors.initials: HM
authors.lastname: Blau
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D001861:Bone Regeneration; D002352:Carrier Proteins / Q000096:biosynthesis*; D015536:Down-Regulation; D050723:Fractures, Bone / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D020869:Gene Expression Profiling; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis; D011859:Radiography; D015398:Signal Transduction; D012886:Skull / Q000000981:diagnostic imaging / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein