SLE-Associated Osteoporosis due to Increased Osteoclast Activity; Decreased Osteoblast Activity

Objectives:

Systemic lupus erythematosus (SLE) is a remitting and relapsing autoimmune disease with varying clinical manifestations that can affect the skin, joints, brain, heart, blood, lungs, kidneys, and oral mucosa. A consequential and potentially preventable disease-related disorder among SLE patients is osteoporosis. However, the bone loss mechanism is still unclear in this abnormal immune condition. Therefore, the purpose of this study is to clarify this mechanism by using a mouse model for SLE.

Methods:

The C3.MRL-Faslpr/J strain (http://jaxmice.jax.org/strain/000480.html) was used as an SLE mouse model. The C3H/HeJ strain, which is a background strain of the SLE mouse model, was used as a control. Bone loss was evaluated by histological analysis. Osteoclast activity was confirmed through two methods: (1) tartrate resistant acid phosphatase (TRAP) staining. (2) ELISA analysis of Receptor Activator for Nuclear Factor kB Ligand (RANKL) concentration in blood serum. Alizarin Red staining was performed to assess the activity of osteoblastic cells which were isolated from bone marrow.

Results:

The trabeculae near the epiphyses of the tibiae and fibulae of SLE model mice were significantly decreased compared to those of the background strain. TRAP positive cell number per bone area and RANKL concentration were significantly increased in SLE model mice. Additionally, bone nodule formation was significantly decreased in SLE model mice.

Conclusion:

The osteoporosis in SLE model mice is due to decreased osteoblast activity and increased osteoclast activity.

This project was funded by grant: NIDCR/NIH R01DE17449