Ren Yinshi, Han Xianglong, Ho Sunita P, Harris Stephen E, Cao Zhengguo, Economides Aris N, Qin Chunlin, Ke Huazhu, Liu Min, Feng Jian Q
*Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA.
*Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, Texas, USA; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China; Department of Preventive and Restorative Dental Sciences, University of California, San Francisco, San Francisco, California, USA; Department of Periodontics, University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA; The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Regeneron Pharmaceuticals, Tarrytown, New York, USA; and Department of Metabolic Disorders, Amgen Incorporated, Thousand Oaks, California, USA
FASEB J. 2015 Jul;29(7):2702-11. doi: 10.1096/fj.14-265496. Epub 2015 Mar 10.
Understanding periodontal ligament (PDL) biology and developing an effective treatment for bone and PDL damage due to periodontitis have been long-standing aims in dental medicine. Here, we first demonstrated by cell lineage tracing and mineral double-labeling approaches that murine PDL progenitor cells display a 2- and 3-fold higher mineral deposition rate than the periosteum and endosteum at the age of 4 weeks, respectively. We next proved that the pathologic changes in osteocytes (Ocys; changes from a spindle shape to round shape with a >50% reduction in the dendrite number/length, and an increase in SOST) are the key pathologic factors responsible for bone and PDL damage in periostin-null mice (a periodontitis animal model) using a newly developed 3-dimensional FITC-Imaris technique. Importantly, we proved that deleting the Sost gene (a potent inhibitor of WNT signaling) or blocking sclerostin function by using the mAb in this periodontitis model significantly restores bone and PDL defects (n = 4-5; P < 0.05). Together, identification of the key contribution of the PDL in normal alveolar bone formation, the pathologic changes of the Ocys in periodontitis bone loss, and the novel link between sclerostin and Wnt signaling in the PDL will aid future drug development in the treatment of patients with periodontitis.
了解牙周膜（PDL）生物学特性并开发针对牙周炎导致的骨和牙周膜损伤的有效治疗方法一直是牙科医学的长期目标。在此，我们首先通过细胞谱系追踪和矿物质双重标记方法证明，在4周龄时，小鼠牙周膜祖细胞的矿物质沉积率分别比骨膜和骨内膜高2倍和3倍。接下来，我们使用新开发的三维FITC-Imaris技术证明，骨细胞的病理变化（从纺锤形变为圆形，树突数量/长度减少>50%，并伴有SOST增加）是骨膜蛋白缺陷小鼠（一种牙周炎动物模型）中导致骨和牙周膜损伤的关键病理因素。重要的是，我们证明在该牙周炎模型中删除Sost基因（一种有效的WNT信号抑制剂）或使用单克隆抗体阻断硬化蛋白功能可显著恢复骨和牙周膜缺陷（n = 4 - 5；P < 0.05）。总之，确定牙周膜在正常牙槽骨形成中的关键作用、牙周炎骨质流失中骨细胞的病理变化以及牙周膜中硬化蛋白与Wnt信号之间的新联系，将有助于未来开发治疗牙周炎患者的药物。
