J. Fosséprez , T. Roels , D. Manicourt , C. Behets
{"title":"Craniofacial dysmorphism of osteogenesis imperfecta mouse and effect of cathepsin K knockout: Preliminary craniometry observations","authors":"J. Fosséprez , T. Roels , D. Manicourt , C. Behets","doi":"10.1016/j.morpho.2024.100785","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><p>In addition to bone fragility, patients with osteogenesis imperfecta (OI) type III have typical craniofacial abnormalities, such as a triangular face and maxillary micrognathism. However, in the osteogenesis imperfecta mouse (oim), a validated model of OI type III, few descriptions exist of craniofacial phenotype. Treatment of OI mostly consists of bisphosphonate administration. Cathepsin K inhibition has been tested as a promising therapeutic approach for osteoporosis and positive results were observed in long bones of cathepsin K knocked out oim (oim/CatK<sup>–/–</sup>). This craniometry study aimed to highlight the craniofacial characteristics of oim and Cathepsin K KO mouse.</p></div><div><h3>Materials and methods</h3><p>We analyzed the craniofacial skeleton of 51 mice distributed in 4 genotype groups: Wt (control), oim, CatK<sup>–/–</sup>, oim/CatK<sup>–/–</sup>. The mice were euthanized at 13 weeks and their heads were analyzed using densitometric (pQCT), X-ray cephalometric, and histomorphometric methods.</p></div><div><h3>Results</h3><p>The craniofacial skeleton of the oim mouse is frailer than the Wt one, with a reduced thickness and mineral density of the cranial vault and mandibular ramus. Different cephalometric data attest a dysmorphism similar to the one observed in humans with OI type III. Those abnormalities were not improved in the oim/CatK<sup>–/–</sup> group.</p></div><div><h3>Conclusion</h3><p>These results suggest that oim mouse could serve as a complete model of the human OI type III, including the craniofacial skeleton. They also suggest that invalidation of cathepsin K has no impact on the craniofacial abnormalities of the oim model.</p></div>","PeriodicalId":39316,"journal":{"name":"Morphologie","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Morphologie","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1286011524000250","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives
In addition to bone fragility, patients with osteogenesis imperfecta (OI) type III have typical craniofacial abnormalities, such as a triangular face and maxillary micrognathism. However, in the osteogenesis imperfecta mouse (oim), a validated model of OI type III, few descriptions exist of craniofacial phenotype. Treatment of OI mostly consists of bisphosphonate administration. Cathepsin K inhibition has been tested as a promising therapeutic approach for osteoporosis and positive results were observed in long bones of cathepsin K knocked out oim (oim/CatK–/–). This craniometry study aimed to highlight the craniofacial characteristics of oim and Cathepsin K KO mouse.
Materials and methods
We analyzed the craniofacial skeleton of 51 mice distributed in 4 genotype groups: Wt (control), oim, CatK–/–, oim/CatK–/–. The mice were euthanized at 13 weeks and their heads were analyzed using densitometric (pQCT), X-ray cephalometric, and histomorphometric methods.
Results
The craniofacial skeleton of the oim mouse is frailer than the Wt one, with a reduced thickness and mineral density of the cranial vault and mandibular ramus. Different cephalometric data attest a dysmorphism similar to the one observed in humans with OI type III. Those abnormalities were not improved in the oim/CatK–/– group.
Conclusion
These results suggest that oim mouse could serve as a complete model of the human OI type III, including the craniofacial skeleton. They also suggest that invalidation of cathepsin K has no impact on the craniofacial abnormalities of the oim model.
目的除骨质脆弱外,成骨不全症(OI)III型患者还有典型的颅面异常,如三角脸和上颌骨小畸形。然而,在成骨不全症小鼠(OI III 型的有效模型 oim)中,关于颅面表型的描述却很少。OI 的治疗主要包括服用双膦酸盐。抑制酪蛋白酶 K 是一种很有前景的骨质疏松症治疗方法,在被酪蛋白酶 K 敲除的 OI(oim/CatK-/-)长骨中观察到了积极的结果。本测颅研究旨在突出 oim 和 Cathepsin K KO 小鼠的颅面特征:我们对51只小鼠的颅面骨骼进行了分析,这些小鼠分为4个基因型组:Wt(对照组)、oim、CatK-/-、oim/CatK-/-。结果 oim小鼠的颅面骨骼比Wt小鼠更脆弱,颅顶和下颌横突的厚度和矿物质密度都有所降低。不同的头颅测量数据证明,小鼠的畸形类似于在患有 OI III 型的人类身上观察到的畸形。这些结果表明,oim 小鼠可作为人类 OI III 型的完整模型,包括颅面部骨骼。这些结果表明,oim 小鼠可作为人类 OI III 型的完整模型,包括颅面部骨骼。这些结果还表明,酪蛋白酶 K 的失效对 oim 模型的颅面部异常没有影响。
期刊介绍:
Morphologie est une revue universitaire avec une ouverture médicale qui sa adresse aux enseignants, aux étudiants, aux chercheurs et aux cliniciens en anatomie et en morphologie. Vous y trouverez les développements les plus actuels de votre spécialité, en France comme a international. Le objectif de Morphologie est d?offrir des lectures privilégiées sous forme de revues générales, d?articles originaux, de mises au point didactiques et de revues de la littérature, qui permettront notamment aux enseignants de optimiser leurs cours et aux spécialistes d?enrichir leurs connaissances.