title: Plasminogen plays a crucial role in bone repair.
abstract: The further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction. Plasminogen is a critical factor of the tissue fibrinolytic system, which mediates tissue repair in the skin and liver. However, the role of the fibrinolytic system in bone regeneration remains unknown. Herein, we investigated bone repair and ectopic bone formation using plasminogen-deficient (Plg⁻/⁻) mice. Bone repair of the femur is delayed in Plg⁻/⁻ mice, unlike that in the wild-type (Plg⁺/⁺) mice. The deposition of cartilage matrix and osteoblast formation were both decreased in Plg⁻/⁻ mice. Vessel formation, macrophage accumulation, and the levels of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) were decreased at the site of bone damage in Plg⁻/⁻ mice. Conversely, heterotopic ossification was not significantly different between Plg⁺/⁺ and Plg⁻/⁻ mice. Moreover, angiogenesis, macrophage accumulation, and the levels of VEGF and TGF-β were comparable between Plg⁺/⁺ and Plg⁻/⁻ mice in heterotopic ossification. Our data provide novel evidence that plasminogen is essential for bone repair. The present study indicates that plasminogen contributes to angiogenesis related to macrophage accumulation, TGF-β, and VEGF, thereby leading to the enhancement of bone repair.
authors: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
authors: Naoyuki
authors: N
authors: Kawao
authors: Yukinori
authors: Y
authors: Tamura
authors: Katsumi
authors: K
authors: Okumoto
authors: Masato
authors: M
authors: Yano
authors: Kiyotaka
authors: K
authors: Okada
authors: Osamu
authors: O
authors: Matsuo
authors: Hiroshi
authors: H
authors: Kaji
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D005260:Female; D005264:Femoral Fractures / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017102:Fracture Healing; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D010958:Plasminogen