biostudies-literatureZieba JNICHD NIH HHSNHLBI NIH HHSNational Institutes of HealthOsteogenesis Imperfecta Foundatione171984https://www.ebi.ac.uk/biostudies/studies/S-EPMC10721276biostudies-literatureUnknown8(21)Osteogenesis imperfecta (OI), or brittle bone disease, is a disorder characterized by bone fragility and increased fracture incidence. All forms of OI also feature short stature, implying an effect on endochondral ossification. Using the Aga2+/- mouse, which has a mutation in type I collagen, we show an affected growth plate primarily due to a shortened proliferative zone. We used single-cell RNA-Seq analysis of tibial and femoral growth plate tissues to understand transcriptional consequences on growth plate cell types. We show that perichondrial cells, which express abundant type I procollagen, and growth plate chondrocytes, which were found to express low amounts of type I procollagen, had ER stress and dysregulation of the same unfolded protein response pathway as previously demonstratJCI insightAltered Sox9 and FGF signaling gene expression in Aga2 OI mice negatively affects linear growth.PMC10721276Geisman Fellowship awardP01 HD0703941R01HL160554R01 HL160554Wachtell DWong SKrakow DKot AZieba JCohn DHMartin JHNevarez LfalseAltered Sox9 and FGF signaling gene expression in Aga2 OI mice negatively affects linear growth.Osteogenesis imperfecta (OI), or brittle bone disease, is a disorder characterized by bone fragility and increased fracture incidence. All forms of OI also feature short stature, implying an effect on endochondral ossification. Using the Aga2+/- mouse, which has a mutation in type I collagen, we show an affected growth plate primarily due to a shortened proliferative zone. We used single-cell RNA-Seq analysis of tibial and femoral growth plate tissues to understand transcriptional consequences on growth plate cell types. We show that perichondrial cells, which express abundant type I procollagen, and growth plate chondrocytes, which were found to express low amounts of type I procollagen, had ER stress and dysregulation of the same unfolded protein response pathway as previously demonstrat2023-01-01T00:00:00Z2023 Nov2026-05-28T19:10:41.571Z2025-04-05T20:12:28.414ZS-EPMC107212763779661510.1172/jci.insight.171984