Characterization of the osteochondral phenotype in human classical osteogenesis imperfecta and in Col1a2oim/oim mice

Osteogenesis imperfecta (OI) is associated with an increased risk of early-onset osteoarthritis (OA); however, it remains unclear whether this risk is driven by underlying osteochondral alterations. Here, we aimed to characterize the osteochondral phenotype in OI to identify osteochondral features that may be relevant to increased OA susceptibility. We collected bilateral tibial plateaus from one adult with classical OI ( COL1A2) who underwent bilateral total knee arthroplasty, and a femoral head from a second adult ( COL1A1) who underwent total hip arthroplasty. The specimens were analyzed using histology and quantitative backscattered electron imaging (qBEI), and the results were compared with those from ten patients with primary knee OA and ten patients with primary hip OA. In addition, we examined hip and knee joints of six-week-old Col1a2 oim/oim mice and wild-type (WT) controls by μCT, histology, and qBEI. In human samples, overall osteochondral morphology was comparable between OI and primary OA, but osteoarthritic subchondral bone in OI showed higher matrix mineralization. Col1a2 oim/oim mice exhibited a pronounced low bone mass phenotype in hip and knee joints, while growth plate architecture and articular cartilage thickness were preserved. However, articular cartilage contained larger chondrocyte clusters, and subchondral trabecular bone showed a hypermineralized and compositionally heterogeneous matrix with increased osteocyte lacunar density. Moreover, the osteocyte lacunocanalicular network was severely disrupted, with shorter canaliculi and fewer canaliculi per osteocyte. Together, these exploratory human case-based observations and juvenile murine data suggest that type I collagen defects are associated with prominent subchondral bone matrix and osteocyte abnormalities alongside altered chondrocyte organization, which together may contribute to joint vulnerability in OI. • Increased OA susceptibility in OI may stem from subchondral bone abnormalities • Human OI samples show high subchondral bone mineralization • Col1a2 oim/oim mice show a low bone mass osteochondral phenotype • Subchondral bone shows altered mineralization and osteocyte network disruption • Articular cartilage in Col1a2 oim/oim mice displays altered chondrocyte organization