Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation.
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.
Wan
Derrick C
DC
Department of Surgery, Stanford University School of Medicine, Stanford University, Stanford, California 94305, USA.
Pomerantz
Jason H
JH
Brunet
Lisa J
LJ
Kim
Jae-Beom
JB
Chou
Yu-Fen
YF
Wu
Benjamin M
BM
Harland
Richard
R
Blau
Helen M
HM
Longaker
Michael T
MT
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
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein