title: Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.
abstract: Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair.
authors: Bone Cell Biology and Imaging Laboratory, Hospital for Special Surgery, New York, NY 10021, USA.
authors: Marie K
authors: MK
authors: Reumann
authors: Olga
authors: O
authors: Strachna
authors: Sarah
authors: S
authors: Yagerman
authors: Daniel
authors: D
authors: Torrecilla
authors: Jihye
authors: J
authors: Kim
authors: Stephen B
authors: SB
authors: Doty
authors: Lyudmila
authors: L
authors: Lukashova
authors: Adele L
authors: AL
authors: Boskey
authors: Philipp
authors: P
authors: Mayer-Kuckuk
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001862:Bone Resorption / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D001842:Bone and Bones / Q000473:pathology*; D002146:Bony Callus / Q000378:metabolism / Q000473:pathology; D051766:Early Growth Response Protein 1 / Q000172:deficiency* / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D017102:Fracture Healing; D050723:Fractures, Bone / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D010027:Osteotomy; D012272:Ribs / Q000601:surgery
chemical_list: D015415:Biomarkers; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D005337:Fibrin