Pulmonary and diaphragmatic pathology in collagen type I alpha 1 mutant mice with osteogenesis imperfecta

作者：Baglole Carolyn J; Liang Feng; Traboulsi Hussein; de Souza Angela Rico; Giordano Christian; Tauer Josephine T; Rauch Frank; Petrof Basil J^*

来源：Pediatric Research, 2018, 83(6): 1165-1171.

DOI：10.1038/pr.2018.36

BACKGROUND: Osteogenesis imperfecta (OI) is most often caused by mutations in type I collagen genes. Respiratory complications have been largely attributed to spine and ribcage deformities. We hypothesized that direct involvement of the pulmonary parenchyma and/or diaphragm by the disease may occur.
METHODS: In Col1a1(Jrt/)(+) mice, a model of severe dominant OI, mean linear intercept length (Lm) was used to assess the distal airspace size. Cross-sectional area (CSA) and myosin heavy chain (MyHC) phenotype of the diaphragm muscle fibers, as well as contractile properties, were determined. OI mice were also treated with neutralizing antibodies against transforming growth factor-beta (TGF-beta).
RESULTS: Distal airspace enlargement occurred in OI mice (Lm +27%). Diaphragmatic thickness and fiber number were reduced, with increases in fast-twitch type IIx/IIb MyHC fibers. Ex vivo force generation (normalized for CSA) of the diaphragm was also significantly reduced. The increased Lm values found in OI mice were not prevented by anti-TGF-beta antibody treatment.
CONCLUSIONS: The Col1a1(Jrt/+) mouse model of OI demon strates: (1) pulmonary airspace enlargement not driven by TGF-beta; and (2) reduced muscle mass and intrinsic contractile weakness of the diaphragm. These results suggest a complex and multifaceted basis for respiratory complications in OI that cannot be solely attributed to bone manifestations.

• 出版日期2018-6
• 单位McGill