Collagen mutation and age contribute to differential craniofacial phenotypes in mouse models of osteogenesis imperfecta

Hsiao H Sung; Wyatt J Spresser; Joseph P Hoffmann; Zongrui Dai; Peter M Van der Kraan; Michelle S Caird; Esmeralda Blaney Davidson; Kenneth M Kozloff

doi:10.1093/jbmrpl/ziad004

Collagen mutation and age contribute to differential craniofacial phenotypes in mouse models of osteogenesis imperfecta

JBMR Plus. 2024 Jan 4;8(1):ziad004. doi: 10.1093/jbmrpl/ziad004. eCollection 2024 Jan.

Authors

Hsiao H Sung^{1

2

3}, Wyatt J Spresser², Joseph P Hoffmann², Zongrui Dai⁴, Peter M Van der Kraan³, Michelle S Caird¹, Esmeralda Blaney Davidson³, Kenneth M Kozloff¹

Affiliations

¹ Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI 48109, United States.
² Department of Oral and Maxillofacial Surgery, University of Michigan, Ann Arbor, MI 48109, United States.
³ Experimental Rheumatology, Department of Rheumatology, Radboud Medical Centre, Nijmegen, The Netherlands, 6525 GA.
⁴ Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, United States.

Abstract

Craniofacial and dentoalveolar abnormalities are present in all types of osteogenesis imperfecta (OI). Mouse models of the disorder are critical to understand 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. The 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-wk-old, 3-mo-old, and 6-mo-old female Brtl/+ and G610c/+ mice. We observed that Brtl/+ skulls are shorter in length than WT (P < .05), whereas G610c/+ skulls are similar in length to their WT counterparts. The 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 < .05). By contrast, G610c/+ mice experience mandibular resorption consistently across all ages, but maxillary resorption is only evident at 6 mo (P < .05). Western blot shows high osteoclastic activities in the Brtl/+ maxilla. Both models exhibit delayed pre-functional eruptions of the third molars (P < .05), which are 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 the 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.

Keywords: alveolar bone; mandible; maxilla; micro-CT imaging; osteogenesis imperfecta; teeth.

Abstract

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