Spatial and temporal changes of subchondral bone proceed to microscopic articular cartilage degeneration in guinea pigs with spontaneous osteoarthritis

Objective: This study aimed to investigate the spatial and temporal subchondral bone change of Dunkin-Hartley (DH) strain guinea pigs spontaneous osteoarthritis (OA) model at early stage with three-dimensional Microfocal Computed Tomography (Micro-CT) analysis, histology and immunohistochemistry. Materials and methods: Knee joints of DH and Bristol Strain 2 (BS2) guinea pigs were analyzed at 1, 2 and 3 months of age for early staged subchondral bone ultrastructure change of OA by Micro-CT and histology. And cartilage degeneration was monitored by histological examination. In addition, expression of Osterix was quantified by immunohistochemistry. Results: Microscopic cartilage degeneration was not found at first 3 months in both DH and BS2 guinea pigs. Subchondral bone sclerosis with trabecular ultrastructure turnover was characterized in subchondral bone of DH guinea pigs. Increased thickness, bone mineral density with decreased porosity were defined in subchondral plate of DH guinea pigs. Subchondral trabecular bone was found to be plate-like, convex and isotropy with higher bone volume. Histology confirmed the finding of lower porosity at osteochondral junction and increased bone volume. Immunohistochemistry revealed that the early OA subchondral bone change may be due to elevated level of osteoblast differentiation. Conclusions: Subchondral bone ultrastructure change occurred at early stage of OA ahead of microscopic cartilage degeneration, which may further impair articular cartilage. It was possibly related to elevated level of osteoblast differentiation.