Plasminogen activator inhibitor-1 deficiency enhances subchondral osteopenia after induction of osteoarthritis in mice.
Plasminogen activator inhibitor-1 deficiency enhances subchondral osteopenia after induction of osteoarthritis in mice.
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DOI：
10.1186/s12891-017-1752-5
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发表时间：
2017-09-11
影响因子：
2.3
通讯作者：
Kaji H
中科院分区：
文献类型：
--
作者：
Moritake A;Kawao N;Okada K;Tatsumi K;Ishida M;Okumoto K;Matsuo O;Akagi M;Kaji H
软骨下骨质减少在骨关节炎（OA）的病理生理学中具有重要意义。尽管先前的研究表明纤溶酶原激活物抑制剂-1（派-1）是一种纤维蛋白溶解抑制剂，与骨代谢有关，但其在OA中的作用仍不清楚。因此，我们研究派-1在OA模型小鼠软骨下骨中的作用。将野生型（WT）和派-1缺陷型（KO）小鼠卵巢切除（OVX），然后进行内侧半月板去稳定化（DMM）手术。在派-1 KO小鼠中，通过定量计算机断层扫描评估，DMM和OVX显著降低了软骨下骨的小梁骨矿物质密度。OVX和/或派-1缺乏对用于评估膝关节退变进展的OARSI评分的影响不显著。派-1缺陷显著增加了IL-1β增强的小鼠原代成骨细胞中受体活化因子核因子κB配体mRNA水平，尽管它不影响成骨细胞的分化。此外，派-1缺乏显着增加破骨细胞形成从小鼠骨髓细胞。我们发现派-1缺乏加速了小鼠OA诱导后的软骨下骨质减少。派-1可能抑制OA诱导后骨吸收的增强和随后的软骨下骨质减少。
Subchondral osteopenia is important for the pathophysiology of osteoarthritis (OA). Although previous studies suggest that plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is related to bone metabolism, its role in OA remains unknown. We therefore investigated the roles of PAI-1 in the subchondral bone in OA model mice. Wild type (WT) and PAI-1-deficient (KO) mice were ovariectomized (OVX), and then destabilization of the medial meniscus (DMM) surgery was performed. DMM and OVX significantly decreased the trabecular bone mineral density of the subchondral bone evaluated by quantitative computed tomography in PAI-1 KO mice. The effects of OVX and/or PAI-1 deficiency on the OARSI score for the evaluation of the progression of knee degeneration were not significant. PAI-1 deficiency significantly augmented receptor activator nuclear factor κB ligand mRNA levels enhanced by IL-1β in mouse primary osteoblasts, although it did not affect osteoblast differentiation. Moreover, PAI-1 deficiency significantly increased osteoclast formation from mouse bone marrow cells. We showed that PAI-1 deficiency accelerates the subchondral osteopenia after induction of OA in mice. PAI-1 might suppress an enhancement of bone resorption and subsequent subchondral osteopenia after induction of OA in mice.
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影响因子：
7
作者：
Pastoureau, P;Leduc, S;De Ceuninck, F
通讯作者：
De Ceuninck, F
影响因子：
2.3
作者：
Miyatake K;Muneta T;Ojima M;Yamada J;Matsukura Y;Abula K;Sekiya I;Tsuji K
通讯作者：
Tsuji K
影响因子：
7
作者：
Srikanth, VK;Fryer, JL;Jones, G
通讯作者：
Jones, G
影响因子：
2.2
作者：
Saito E;Suzuki D;Kurotaki D;Mochizuki A;Manome Y;Suzawa T;Toyoshima Y;Ichikawa T;Funatsu T;Inoue T;Takami M;Tamura T;Inagaki K;Kamijo R
通讯作者：
Kamijo R
影响因子：
7
作者：
Bertuglia, A.;Lacourt, M.;Laverty, S.
通讯作者：
Laverty, S.