Transcriptional profiling of otic capsule and femur in the oim mouse model of osteogenesis imperfecta.

Hearing loss is a common and debilitating complication of the brittle bone disorder osteogenesis imperfecta (OI). Existing treatments that are designed to address age-related hearing loss in the broader population do not meet the needs of OI patients, who exhibit skeletal fragility and begin to lose their hearing when they are young-adults. The biologic mechanisms responsible for hearing loss in OI are unknown, hindering the development of preventative therapies. To identify potential mechanisms that drive this condition, we performed transcriptome profiling on femoral and otic capsule specimens obtained from the Col1a2oim mouse model at 12- and 25-wk of age. We found that the bulk transcriptomes of femora and otic capsules were markedly different, regardless of mouse genotype. Further, bone formation-associated transcripts were reduced at 25-wk, compared to 12-wk. Mice homozygous for the oim mutation exhibited increased abundance of transcripts associated with osteoblast activity and type I collagen production compared to WT mice in both femoral and otic capsule specimens. The most notable difference between oim and WT mouse otic capsules was the depletion of the transcripts that encode mucin and keratin, suggesting dysregulation of epithelial cells, which has been previously linked to hearing loss. Our data offer new insights into the mechanisms that disrupt the middle ear in OI. Analysis of epithelial cells obtained from OI patients and additional models of OI could suggest novel strategies to prevent and/or treat hearing loss.