title: BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing.
abstract: Adult bones have a notable regenerative capacity. Over 40 years ago, an intrinsic activity capable of initiating this reparative response was found to reside within bone itself, and the term bone morphogenetic protein (BMP) was coined to describe the molecules responsible for it. A family of BMP proteins was subsequently identified, but no individual BMP has been shown to be the initiator of the endogenous bone repair response. Here we demonstrate that BMP2 is a necessary component of the signaling cascade that governs fracture repair. Mice lacking the ability to produce BMP2 in their limb bones have spontaneous fractures that do not resolve with time. In fact, in bones lacking BMP2, the earliest steps of fracture healing seem to be blocked. Although other osteogenic stimuli are still present in the limb skeleton of BMP2-deficient mice, they cannot compensate for the absence of BMP2. Collectively, our results identify BMP2 as an endogenous mediator necessary for fracture repair.
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tsuji
authors.forename: Amitabha
authors.initials: A
authors.lastname: Bandyopadhyay
authors.forename: Brian D
authors.initials: BD
authors.lastname: Harfe
authors.forename: Karen
authors.initials: K
authors.lastname: Cox
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kakar
authors.forename: Louis
authors.initials: L
authors.lastname: Gerstenfeld
authors.forename: Thomas
authors.initials: T
authors.lastname: Einhorn
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Tabin
authors.forename: Vicki
authors.initials: V
authors.lastname: Rosen
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D017102:Fracture Healing / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta