α2-antiplasmin modulates bone formation by negatively regulating osteoblast differentiation and function

Kanno,Yosuke; Ishisaki,Akira; Kuretake,Hiromi; Maruyama,Chihiro; Matsuda,Ayaka; Matsuo,Osamu

doi:10.3892/ijmm.2017.3055

α2-antiplasmin modulates bone formation by negatively regulating osteoblast differentiation and function

Authors:
- Yosuke Kanno
- Akira Ishisaki
- Hiromi Kuretake
- Chihiro Maruyama
- Ayaka Matsuda
- Osamu Matsuo
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Affiliations: Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyoto 610-0395, Japan, Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Iwate 028-3694, Japan, Kindai University Faculty of Medicine, Osaka 589-8511, Japan
Published online on: July 5, 2017 https://doi.org/10.3892/ijmm.2017.3055
Pages: 854-858

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Abstract

α2-antiplasmin (α2AP) is known to be a physiological inhibitor of plasmin. Previously, we showed that α2AP displays various functions, such as promotion of extracellular matrix production, cell growth, and cell differentiation that are not promoted by its function as a plasmin inhibitor. We herein investigated the role of α2AP in bone formation by examining calcein incorporation after its injection in α2AP-deficient mice. We found that α2AP deficiency enhanced the bone formation rate in mice. We also found that the osteocalcin expression and alkaline phosphatase activity were elevated in the femur and serum of the α2AP-deficient mice. Intriguingly, α2AP deficiency promoted osteoblast (OB) differentiation of primary calvarial OBs. In contrast, α2AP attenuated OB differentiation of mouse osteoblastic the MC3T3-E1 cells. Furthermore, α2AP attenuated Wnt-3a-induced β-catenin expression and low‑density lipoprotein receptor-related protein 6 activation in the MC3T3-E1 cells. These results suggest that α2AP negatively affects OB differentiation and function by inhibiting the Wnt/β-catenin pathway. These findings provide a basis for clinical strategies to improve various bone disorders.

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