Hsiao H Sung, Wyatt Spresser, Joseph P Hoffmann, Zongrui Dai, Peter M Van der Kraan, M. Caird, Esmeralda Blaney Davidson, K. Kozloff
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We performed morphological measurements on the micro-CT scanned heads of 3-week-old, 3-month-old, and 6-month-old female Brtl/+ and G610c/+ mice. We observed that Brtl/+ skulls are shorter in length than WT (p < 0.05), whereas G610c/+ skulls are similar in length to their WT counterparts. Brtl/+ mice exhibit alveolar bone with a porotic-like appearance that is not observed in G610c/+. As they age, Brtl/+ mice show severe bone resorption in both the maxilla and mandible (p < 0.05). In contrast, G610c/+ mice experience mandibular resorption consistently across all ages, but maxillary resorption is only evident at 6 months (p < 0.05). Western blot shows high osteoclastic activities in the Brtl/+ maxilla. Both models exhibit delayed pre-functional eruptions of the third molars (p < 0.05), similar to those observed in some bisphosphonate-treated OI subjects. Our study shows that the Brtl/+ and G610c/+ mice display clear features found in type IV OI patients; both show age-related changes in craniofacial growth phenotype. Therefore, understanding the craniofacial features of these models and how they age will allow us to select the most accurate mouse model, mouse age, and bone structure for the specific craniofacial bone treatment of differing OI groups.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Collagen mutation and age contribute to differential craniofacial phenotypes in mouse models of osteogenesis imperfecta\",\"authors\":\"Hsiao H Sung, Wyatt Spresser, Joseph P Hoffmann, Zongrui Dai, Peter M Van der Kraan, M. Caird, Esmeralda Blaney Davidson, K. 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引用次数: 0
摘要
所有类型的成骨不全症(OI)都存在颅面和牙槽骨异常。该疾病的小鼠模型对于了解这些异常和潜在的 OI 发病机制至关重要。以前对严重受影响的 OI 小鼠进行的研究报告了广泛的颅面表型,与人类疾病有一些相似之处。Brtl/+ 和 G610c/+ 分别属于中度严重和轻度 IV 型 OI。人们对这些模型对颅面部骨骼的老化影响及其与人类 OI 的同源性知之甚少。本研究旨在分析Brtl/+和G610c/+在衰老过程中的颅面形态,以确定是否适合进一步的OI颅面骨骼干预研究。我们对 3 周大、3 个月大和 6 个月大的雌性 Brtl/+ 和 G610c/+ 小鼠的头部进行了微计算机断层扫描形态测量。我们观察到 Brtl/+ 头骨的长度比 WT 小鼠短(p < 0.05),而 G610c/+ 头骨的长度与 WT 小鼠相似。Brtl/+ 小鼠的牙槽骨呈现出多孔状外观,而 G610c/+ 则没有这种现象。随着年龄的增长,Brtl/+小鼠的上颌骨和下颌骨都出现了严重的骨吸收现象(p < 0.05)。相比之下,G610c/+ 小鼠在所有年龄段都会出现下颌骨吸收,但上颌骨吸收只在 6 个月时才明显(p < 0.05)。Western 印迹显示 Brtl/+ 上颌骨的破骨活性很高。两种模型都表现出第三磨牙功能前萌出延迟(p < 0.05),这与在一些接受过双磷酸盐治疗的 OI 受试者身上观察到的情况类似。我们的研究表明,Brtl/+ 和 G610c/+ 小鼠表现出 IV 型 OI 患者的明显特征;两者的颅面生长表型都出现了与年龄相关的变化。因此,了解这些模型的颅面特征及其如何衰老将使我们能够选择最准确的小鼠模型、小鼠年龄和骨结构,以针对不同的 OI 群体进行特定的颅面骨治疗。
Collagen mutation and age contribute to differential craniofacial phenotypes in mouse models of osteogenesis imperfecta
Craniofacial and dentoalveolar abnormalities are present in all types of Osteogenesis Imperfecta (OI). Mouse models of the disorder are critical to understanding these abnormalities and underlying OI pathogenesis. Previous studies on severely affected OI mice report a broad spectrum of craniofacial phenotypes, exhibiting some similarities to the human disorder. Brtl/+ and G610c/+ are moderately severe and mild type IV OI, respectively. Little is known about the aging effects on the craniofacial bones of these models and their homology to human OI. This study aimed to analyze the Brtl/+ and G610c/+ craniofacial morphometries during aging to establish suitability for further OI craniofacial bone intervention studies. We performed morphological measurements on the micro-CT scanned heads of 3-week-old, 3-month-old, and 6-month-old female Brtl/+ and G610c/+ mice. We observed that Brtl/+ skulls are shorter in length than WT (p < 0.05), whereas G610c/+ skulls are similar in length to their WT counterparts. Brtl/+ mice exhibit alveolar bone with a porotic-like appearance that is not observed in G610c/+. As they age, Brtl/+ mice show severe bone resorption in both the maxilla and mandible (p < 0.05). In contrast, G610c/+ mice experience mandibular resorption consistently across all ages, but maxillary resorption is only evident at 6 months (p < 0.05). Western blot shows high osteoclastic activities in the Brtl/+ maxilla. Both models exhibit delayed pre-functional eruptions of the third molars (p < 0.05), similar to those observed in some bisphosphonate-treated OI subjects. Our study shows that the Brtl/+ and G610c/+ mice display clear features found in type IV OI patients; both show age-related changes in craniofacial growth phenotype. Therefore, understanding the craniofacial features of these models and how they age will allow us to select the most accurate mouse model, mouse age, and bone structure for the specific craniofacial bone treatment of differing OI groups.