title: α₂-Antiplasmin is involved in bone loss induced by ovariectomy in mice.
abstract: The mechanism of postmenopausal osteoporosis is not fully understood. α2-Antiplasmin (α2-AP) is the primary inhibitor of plasmin in the fibrinolytic system, but is known to have activities beyond fibrinolysis. However, its role in bone metabolism and the pathogenesis of osteoporosis remains unknown. In the current study, we therefore examined the effects of α2-AP deficiency on ovariectomy (OVX)-induced bone loss by using wild-type and α2-AP-deficient mice. Quantitative computed tomography analysis revealed that α2-AP deficiency blunted OVX-induced trabecular bone loss in mice. Moreover, α2-AP deficiency significantly blunted serum levels of bone-specific alkaline phosphatase, cross-linked C-telopeptide of type I collagen, and interleukin (IL)-1β elevated by OVX. α2-AP treatment elevated the levels of IL-1β and tumor necrosis factor (TNF)-α mRNA in RAW 264.7 cells, although it suppressed osteoclast formation induced by receptor activator of nuclear factor-κB ligand. α2-AP treatment activated ERK1/2 and p38 MAP kinase pathways in RAW 264.7 cells, and these MAP kinase inhibitors antagonized the levels of IL-1β mRNA elevated by α2-AP. The data demonstrate that α2-AP is linked to bone loss due to OVX, through a mechanism that depends in part on the production of IL-1β and TNF-α in monocytes.
authors.affiliation: Department of Orthopaedic Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan; Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Shiomi
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kawao
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yano
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okada
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Life Science Research Institute, Kinki University, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Okumoto
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
authors.affiliation: Department of Orthopaedic Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Akagi
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan. Electronic address: hkaji@med.kindai.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaji
mesh_terms: D000818:Animals; D000933:Antifibrinolytic Agents / Q000378:metabolism*; D015153:Blotting, Western; D001842:Bone and Bones / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism*; D010052:Ovariectomy; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000933:Antifibrinolytic Agents; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Bone; Estrogen; Interleukin-1β; Osteoporosis; α(2)-Antiplasmin