Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA.
Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
J Bone Miner Res. 2023 Aug;38(8):1192-1207. doi: 10.1002/jbmr.4829. Epub 2023 May 27.
Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD-MBD) describes the dysregulation of mineral homeostasis, including hyperphosphatemia and elevated parathyroid hormone (PTH) secretion, skeletal abnormalities, and vascular calcification. CKD-MBD impacts the oral cavity, with effects including salivary gland dysfunction, enamel hypoplasia and damage, increased dentin formation, decreased pulp volume, pulp calcifications, and altered jaw bones, contributing to clinical manifestations of periodontal disease and tooth loss. Underlying mechanisms are not fully understood, and CKD mouse models commonly require invasive procedures with high rates of infection and mortality. We aimed to characterize the dentoalveolar effects of an adenine diet (AD)-induced CKD (AD-CKD) mouse model. Eight-week-old C57BL/6J mice were provided either a normal phosphorus diet control (CTR) or adenine and high-phosphorus diet CKD to induce kidney failure. Mice were euthanized at 15 weeks old, and mandibles were collected for micro-computed tomography and histology. CKD mice exhibited kidney failure, hyperphosphatemia, and hyperparathyroidism in association with porous cortical bone in femurs. CKD mice showed a 30% decrease in molar enamel volume compared to CTR mice. Enamel wear was associated with reduced ductal components, ectopic calcifications, and altered osteopontin (OPN) deposition in submandibular salivary glands of CKD mice. Molar cusps in CKD mice were flattened, exposing dentin. Molar dentin/cementum volume increased 7% in CKD mice and pulp volume decreased. Histology revealed excessive reactionary dentin and altered pulp-dentin extracellular matrix proteins, including increased OPN. Mandibular bone volume fraction decreased 12% and bone mineral density decreased 9% in CKD versus CTR mice. Alveolar bone in CKD mice exhibited increased tissue-nonspecific alkaline phosphatase localization, OPN deposition, and greater osteoclast numbers. AD-CKD recapitulated key aspects reported in CKD patients and revealed new insights into CKD-associated oral defects. This model has potential for studying mechanisms of dentoalveolar defects or therapeutic interventions. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
慢性肾脏病（CKD）的特征是肾脏损伤和肾功能丧失。CKD 矿物质和骨代谢紊乱（CKD-MBD）描述了矿物质稳态的失调，包括高磷血症和甲状旁腺激素（PTH）分泌增加、骨骼异常和血管钙化。CKD-MBD 会影响口腔，导致唾液腺功能障碍、釉质发育不全和损伤、牙本质形成增加、牙髓体积减少、牙髓钙化和颌骨改变，导致牙周病和牙齿脱落的临床表现。其潜在机制尚不完全清楚，且 CKD 小鼠模型通常需要进行具有高感染和死亡率的侵入性手术。我们旨在描述腺嘌呤饮食（AD）诱导的 CKD（AD-CKD）小鼠模型的牙牙槽效应。将 8 周龄 C57BL/6J 小鼠分别给予正常磷饮食对照（CTR）或腺嘌呤和高磷饮食 CKD，以诱导肾衰竭。15 周龄时处死小鼠，采集下颌骨进行微计算机断层扫描和组织学检查。CKD 小鼠表现出肾衰竭、高磷血症和甲状旁腺功能亢进，同时伴有股骨多孔皮质骨。与 CTR 小鼠相比，CKD 小鼠的磨牙釉质体积减少了 30%。釉质磨损与下颌下唾液腺导管成分减少、异位钙化和骨桥蛋白（OPN）沉积改变有关。CKD 小鼠的磨牙牙尖变平，露出牙本质。CKD 小鼠的磨牙牙本质/牙骨质体积增加了 7%，牙髓体积减少。组织学显示反应性牙本质过多，牙髓-牙本质细胞外基质蛋白改变，包括 OPN 增加。与 CTR 小鼠相比，CKD 小鼠的下颌骨体积分数减少了 12%，骨密度减少了 9%。CKD 小鼠的牙槽骨表现出组织非特异性碱性磷酸酶定位增加、OPN 沉积增加和破骨细胞数量增加。AD-CKD 重现了 CKD 患者报告的关键方面，并揭示了 CKD 相关口腔缺陷的新见解。该模型具有研究牙牙槽缺陷或治疗干预机制的潜力。© 2023 作者。《骨与矿物质研究杂志》由 Wiley 期刊出版公司代表美国骨与矿物质研究协会（ASBMR）出版。
