Locally Secreted Semaphorin 4D Is Engaged in Both Pathogenic Bone Resorption and Retarded Bone Regeneration in a Ligature-Induced Mouse Model of Periodontitis.
Locally Secreted Semaphorin 4D Is Engaged in Both Pathogenic Bone Resorption and Retarded Bone Regeneration in a Ligature-Induced Mouse Model of Periodontitis.
复制标题
DOI：
10.3390/ijms23105630
复制
发表时间：
2022-05-18
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
众所周知，脑信号蛋白4D（Sema 4D）通过与成骨细胞上表达的丛蛋白B1结合来抑制IGF-1介导的成骨。然而，它在牙周炎患者的龈沟液中的水平升高，并且在破骨细胞介导的牙周骨吸收的潜在上调的背景下其活动的范围更广，这表明需要进一步研究这种多方面的分子。总之，Sema 4D在牙周炎中的病理生理作用需要进一步研究。因此，将结扎线连接到小鼠上颌磨牙7天诱导牙槽骨吸收，伴有局部升高的可溶性Sema 4D（sSema 4D）、TNF-α和RANKL。在接下来的14天内，去除结扎线诱导自发性骨再生，这被抗Sema 4D-mAb给药显著促进。抗Sema 4D-mAb在体外破骨细胞生成和窝形成中也受到RANKL刺激的BMMC的抑制。虽然抗Sema 4D-mAb下调了小鼠牙周炎诱导的骨吸收，但它既不影响局部TNF-α和RANKL的产生，也不影响全身骨骼骨重建。RANKL诱导的破骨细胞生成和再吸收活性也受到CD 72阻断的抑制，但丛蛋白B2没有，这表明破骨细胞释放的sSema 4D通过与CD 72受体连接促进破骨细胞生成。总的来说，我们的数据表明，破骨细胞释放的ssSema 4D可能通过减少骨形成，同时上调骨吸收发挥双重功能。
It is well known that Semaphorin 4D (Sema4D) inhibits IGF-1-mediated osteogenesis by binding with PlexinB1 expressed on osteoblasts. However, its elevated level in the gingival crevice fluid of periodontitis patients and the broader scope of its activities in the context of potential upregulation of osteoclast-mediated periodontal bone-resorption suggest the need for further investigation of this multifaceted molecule. In short, the pathophysiological role of Sema4D in periodontitis requires further study. Accordingly, attachment of the ligature to the maxillary molar of mice for 7 days induced alveolar bone-resorption accompanied by locally elevated, soluble Sema4D (sSema4D), TNF-α and RANKL. Removal of the ligature induced spontaneous bone regeneration during the following 14 days, which was significantly promoted by anti-Sema4D-mAb administration. Anti-Sema4D-mAb was also suppressed in vitro osteoclastogenesis and pit formation by RANKL-stimulated BMMCs. While anti-Sema4D-mAb downmodulated the bone-resorption induced in mouse periodontitis, it neither affected local production of TNF-α and RANKL nor systemic skeletal bone remodeling. RANKL-induced osteoclastogenesis and resorptive activity were also suppressed by blocking of CD72, but not Plexin B2, suggesting that sSema4D released by osteoclasts promotes osteoclastogenesis via ligation to CD72 receptor. Overall, our data indicated that ssSema4D released by osteoclasts may play a dual function by decreasing bone formation, while upregulating bone-resorption.
登录
查看更多内容
影响因子：
9.8
作者：
Filipowska J;Tomaszewski KA;Niedźwiedzki Ł;Walocha JA;Niedźwiedzki T
通讯作者：
Niedźwiedzki T
影响因子：
8.3
作者：
Chen Y;Zhang L;Liu WX;Wang K
通讯作者：
Wang K
影响因子：
6
作者：
Kim JM;Lin C;Stavre Z;Greenblatt MB;Shim JH
通讯作者：
Shim JH
DOI：
10.1093/rheumatology/keq031
发表时间：
2010-07
期刊：
Rheumatology (Oxford, England)
影响因子：
--
作者：
Horiuchi T;Mitoma H;Harashima S;Tsukamoto H;Shimoda T
通讯作者：
Shimoda T
影响因子：
--
作者：
Kawai, T.;Paster, B. J.;Taubman, M. A.
通讯作者：
Taubman, M. A.