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Sclerostin antibody improves alveolar bone quality in the Hyp mouse model of X-linked hypophosphatemia (XLH)
International Journal of Oral Science ( IF 14.9 ) Pub Date : 2023-10-10 , DOI: 10.1038/s41368-023-00252-1
Kelsey A Carpenter 1 , Delia O Alkhatib 1 , Bryan A Dulion 1 , Elizabeth Guirado 2 , Shreya Patel 1 , Yinghua Chen 2 , Anne George 2 , Ryan D Ross 1, 3, 4
Affiliation  

X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg−1 of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.



中文翻译:

Sclerostin 抗体可改善 X 连锁低磷血症 (XLH) Hyp 小鼠模型中的牙槽骨质量

X 连锁低磷血症 (XLH) 是一种罕见疾病,因成纤维细胞生长因子 23 (FGF23) 生成升高,导致低磷血症以及骨骼和牙齿矿化受损。XLH 的临床表现包括牙脓肿和牙周病的高发病率,这可能是由牙槽骨复合体(包括牙槽骨、牙骨质、牙本质和牙周膜)结构不良引起的。我们之前的研究表明,硬化素抗体 (Scl-Ab) 治疗可改善XLH Hyp小鼠模型中磷酸盐稳态,并增加长骨质量、强度和矿化。在当前的研究中,我们研究了 Scl-Ab 是否影响Hyp小鼠的牙槽结构。从12周龄开始,雄性和雌性野生型和Hyp同窝仔鼠每周两次注射25mg·kg -1媒介物或Scl-Ab,并在20周龄时安乐死。Scl-Ab 增加了雄性和雌性小鼠的牙槽骨质量以及雄性小鼠的牙槽组织矿物质密度。Scl-Ab 的积极作用与活性(非磷酸化)β-连环蛋白、牙本质基质蛋白 1 (DMP1) 和骨桥蛋白染色的牙槽骨细胞比例的增加一致。Scl-Ab 对牙本质、牙釉质、无细胞或细胞牙骨质的质量和矿化没有影响。Hyp 小鼠牙周膜 (PDL) 附着分数增加的趋势不显着。其他 PDL 纤维结构参数不受 Scl-Ab 影响。目前的研究表明,Scl-Ab 可以改善成年Hyp小鼠的牙槽骨。

更新日期:2023-10-10
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