Processes of Osteophyte Formation in Guinea Pigs with Spontaneous Osteoarthritis

In this study, we investigated osteophyte formation processes in guinea pigs with spontaneous osteoarthritis, histochemically and immunohistochemically. Serial thin frontal sections of right knee joints were prepared from Hartley guinea pigs aged 1, 3, 5, 8, 12 and 18 months. The severity of osteoarthritis was evaluated by safranin-O staining, and the animals were classified into 3 groups: mild, moderate and severe. In addition, immunostaining was performed by using primary antibodies against the proliferating cell nuclear antigen (PCNA), type-I, -II and -III collagens, insulin-like growth factor 1 (IGF-1) and IGF-1 receptor. In the mild group, there was fibrous connective tissue continuous with the synovial membrane and covering the margins of the articular cartilage of the medial tibial condyle. This tissue contained spindle-shaped fibroblastic-like cells. These cells were positive for PCNA, type-I and -III collagens, IGF-1 and IGF-1 receptor. In the moderate group, the chondrocytes beneath the fibroblastic-like cell layer had proliferated and were clustered together. These chondrocytes were also positive for PCNA, type-I and -III collagens, IGF-1 and IGF-1 receptor. In the severe group, this marginal area had been replaced by type-II collagen-positive chondrophytes, which further changed to osteophytes due to the process of endochondral ossification. In guinea pigs, fibroblastic-like cells at the margins of the articular cartilage of the knee joints seemed to be totipotent immature mesenchymal cells. These cells may be the precursors of osteophytes, and IGF-1 appears to be involved in their formation.