Sclerostin antibody improves alveolar bone quality in the Hyp mouse model of X-linked hypophosphatemia (XLH).

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Kelsey A Carpenter, Delia O Alkhatib, Bryan A Dulion, Elizabeth Guirado, Shreya Patel, Yinghua Chen, Anne George, Ryan D Ross
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Abstract

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.

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在X连锁低磷血症(XLH)的Hyp小鼠模型中,硬化蛋白抗体可改善牙槽骨质量。
X连锁低磷血症(XLH)是一种罕见的成纤维细胞生长因子23(FGF23)产生增加的疾病,可导致低磷血症和骨和牙齿矿化受损。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-牙槽复合体的不良结构引起的,包括牙槽骨、牙骨质、牙本质和牙周膜。我们之前的研究表明,硬化素抗体(Scl-Ab)治疗改善了XLH Hyp小鼠模型中的磷酸盐稳态,并增加了长骨质量、强度和矿化。在目前的研究中,我们研究了Scl-Ab是否会影响Hyp小鼠的齿杆结构。雄性和雌性野生型和Hyp同窝仔注射25 mg·kg-1的载体或Scl-Ab,从12周龄开始每周两次,并在20周龄时实施安乐死。Scl-Ab增加了雄性和雌性小鼠的肺泡骨量和雄性小鼠的肺泡组织矿物质密度。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)和骨桥蛋白染色的肺泡骨细胞的比例增加一致。Scl-Ab对牙本质、牙釉质、脱细胞或细胞牙骨质的质量和矿化没有影响。在Hyp小鼠体内,牙周膜(PDL)附着分数增加的趋势并不显著。附加的PDL纤维结构参数不受Scl-Ab的影响。目前的研究表明Scl-Ab可以改善成年Hyp小鼠的牙槽骨。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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