Distinct type I collagen alterations cause intrinsic lung and respiratory defects of variable severity in mouse models of osteogenesis imperfecta.

Autor: Dimori M; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Fett J; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Leikin S; Section on Physical Biochemistry, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, USA., Otsuru S; Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA., Thostenson JD; Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Carroll JL; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Morello R; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.; Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA.; Division of Genetics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Jazyk: angličtina
Zdroj: The Journal of physiology [J Physiol] 2023 Jan; Vol. 601 (2), pp. 355-379. Date of Electronic Publication: 2022 Nov 09.
DOI: 10.1113/JP283452
Abstrakt: Type I collagen alterations cause osteogenesis imperfecta (OI), a connective tissue disorder characterized by severe bone fragility. Patients with OI can suffer from significant pulmonary manifestations including severe respiratory distress in the neonatal period and a progressive decline in respiratory function in adulthood. We and others have shown intrinsic lung defects in some mouse models of OI. In this large study, we performed histological, histomorphometric, microcomputed tomography and invasive studies on oim/+, Col1a2 +/G610C , CrtapKO and oim/oim mice, mimicking mild to moderate to severe OI, with the overall goal of determining the extent of their pulmonary and respiratory mechanics defects and whether these defects correlate with the skeletal disease severity and affect each sex equally. Although with variable severity, OI lung histology consistently showed alveolar simplification with enlarged acinar airspace and reduced alveolar surface. Numerous respiratory mechanics parameters, including respiratory system resistance and elastance, tissue damping, inspiratory capacity, total lung capacity, and others, were significantly and similarly impacted in CrtapKO and oim/oim but not in oim/+ or Col1a2 +/G610C compared to control mice. Our data indicate that the impact of type I collagen alterations and OI on lung morphology and function positively correlate with the severity of the extracellular matrix deficiency. Moreover, the respiratory defects were more pronounced in male compared to female mice. It will be important to determine whether our observations in mice translate to OI patients and to dissect the respective contribution of intrinsic lung defects vs. extrinsic skeletal defects to impaired lung function in OI. KEY POINTS: Different type I collagen alterations in mouse models of osteogenesis imperfecta (OI) cause similar abnormal lung histology, with alveolar simplification and reduced alveolar surface, reminiscent of emphysema. Several respiratory mechanics parameters are altered in mouse models of OI. The impact of type I collagen alterations and OI on lung morphology and function positively correlate with the severity of the extracellular matrix deficiency. Respiratory defects were more pronounced in male compared to female mice. It will be important to determine whether our observations in mice translate to OI patients and to dissect the respective contribution of intrinsic lung defects vs. extrinsic skeletal defects to impaired lung function in OI.
(© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)
Databáze: MEDLINE
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