*4.4. CIA Rat Model Combined with Bone Injury Model*

Twenty-one days after arthritis induction, a critical size femur defect was performed in 5 CIA rats, as previously described by our group [30]. Briefly, knees were shaved and disinfected, and then an incision was made in the skin and muscles surrounding the right femur were retracted. After lateral knee arthrotomy, a cylindrical defect (FD, 3 × 4 mm, diameter × depth) was created using a surgical drill (micromotor, K-control TLC 4965) in the anterolateral wall of the lateral condyle of the femur. Surgeries were performed under general anesthesia with volatile isoflurane. After surgery, analgesia was provided by subcutaneous administration of buprenorphine (0.05 mg/kg) twice a day. Three days after the bone injury, animals were euthanized for blood and organ collection.
