Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
Bone. 2018 Feb;107:196-207. doi: 10.1016/j.bone.2017.12.004. Epub 2017 Dec 5.
The periodontal complex is essential for tooth attachment and function and includes the mineralized tissues, cementum and alveolar bone, separated by the unmineralized periodontal ligament (PDL). To gain insights into factors regulating cementum-PDL and bone-PDL borders and protecting against ectopic calcification within the PDL, we employed a proteomic approach to analyze PDL tissue from progressive ankylosis knock-out (Ank) mice, featuring reduced PP, rapid cementogenesis, and excessive acellular cementum. Using this approach, we identified the matrix protein osteopontin (Spp1/OPN) as an elevated factor of interest in Ank mouse molar PDL. We studied the role of OPN in dental and periodontal development and function. During tooth development in wild-type (WT) mice, Spp1 mRNA was transiently expressed by cementoblasts and strongly by alveolar bone osteoblasts. Developmental analysis from 14 to 240days postnatal (dpn) indicated normal histological structures in Spp1 comparable to WT control mice. Microcomputed tomography (micro-CT) analysis at 30 and 90dpn revealed significantly increased volumes and tissue mineral densities of Spp1 mouse dentin and alveolar bone, while pulp and PDL volumes were decreased and tissue densities were increased. However, acellular cementum growth was unaltered in Spp1 mice. Quantitative PCR of periodontal-derived mRNA failed to identify potential local compensators influencing cementum in Spp1 vs. WT mice at 26dpn. We genetically deleted Spp1 on the Ank mouse background to determine whether increased Spp1/OPN was regulating periodontal tissues when the PDL space is challenged by hypercementosis in Ank mice. Ank; Spp1 double deficient mice did not exhibit greater hypercementosis than that in Ank mice. Based on these data, we conclude that OPN has a non-redundant role regulating formation and mineralization of dentin and bone, influences tissue properties of PDL and pulp, but does not control acellular cementum apposition. These findings may inform therapies targeted at controlling soft tissue calcification.
牙周复合体对于牙齿的附着和功能至关重要，它包括矿化组织、牙骨质和牙槽骨，由未矿化的牙周韧带 (PDL) 分隔。为了深入了解调节牙骨质-PDL 和骨-PDL 边界的因素，并防止 PDL 内异位钙化，我们采用蛋白质组学方法分析了进展性粘连敲除 (Ank) 小鼠的牙周韧带组织，其特征是 PP 减少、快速牙骨质形成和大量无细胞牙骨质。使用这种方法，我们确定基质蛋白骨桥蛋白 (Spp1/OPN) 是 Ank 小鼠磨牙牙周韧带中升高的感兴趣因素。我们研究了 OPN 在牙齿和牙周发育和功能中的作用。在野生型 (WT) 小鼠的牙齿发育过程中，Spp1 mRNA 短暂地由牙骨质细胞表达，并强烈地由牙槽骨成骨细胞表达。从出生后 14 至 240 天 (dpn) 的发育分析表明，Spp1 的组织学结构与 WT 对照小鼠正常。30 和 90 dpn 的微计算机断层扫描 (micro-CT) 分析显示，Spp1 小鼠牙本质和牙槽骨的体积和组织矿物质密度显著增加，而牙髓和 PDL 的体积减少，组织密度增加。然而，Spp1 小鼠的无细胞牙骨质生长没有改变。在 Spp1 与 WT 小鼠中，牙周来源的 mRNA 的定量 PCR 未能鉴定出潜在的局部补偿因子，这些因子影响 26 dpn 时的牙骨质。我们在 Ank 小鼠背景上遗传缺失 Spp1，以确定当 Ank 小鼠的 PDL 空间受到 hypercementosis 挑战时，增加的 Spp1/OPN 是否调节牙周组织。与 Ank 小鼠相比，Ank; Spp1 双缺失小鼠没有表现出更大的 hypercementosis。基于这些数据，我们得出结论，OPN 在调节牙本质和骨的形成和矿化、影响 PDL 和牙髓的组织特性方面具有非冗余作用，但不能控制无细胞牙骨质附着。这些发现可能为靶向控制软组织钙化的治疗提供信息。
