Analysis of Osteoclast Activation in the Pathogenesis of Rheumatoid Arthritis

Objectives: Although osteoclasts (OCs) are known to play a key role in the pathogenesis of rheumatoid arthritis (RA), the precise mechanism how OCs are activated in RA has been still obscured. In this study, we investigated functions of OCs using MRL/lpr mice, one of animal models for human RA. Methods: Bone marrow-derived OCs (BMOCs) were generated by the culture with M-CSF and RANKL, and their phenotypes or functions were analyzed by flow cytometry, pit formation assay, and real-time RT-PCR. In vivo bone dynamics was scanned using a micro CT system, and investigated by pathological and biochemical analyses. Results: The bone findings of MRL/lpr mice showed the decreased bone density like an osteoporosis. The number of mature BMOCs from MRL/lpr mice was significantly increased compared with those from control MRL+/+ mice. Pit formation assay revealed that function of BMOCs from MRL/lpr mice was more enhanced than that from control mice. The mRNA expressions of OC markers such as cathepsin K and tartrate-resistant acid phosphatase (TRAP) from MRL/lpr mice were increased compared with those from control mice. In addition, the mRNA expression of apoptosis-related genes including second mitochondria-derived activator of caspase (Smac)/ direct inhibitor of apoptosis-binding protein with low pl (DIABLO) of BMOCs from MRL/lpr mice was significantly decreased in contrast to control BMOCs. Conclusions: Enhanced activation of OCs in MRL/lpr mice might be associated the pathogenesis for RA with bone destruction.