Introduction: Recent studies have revealed that rapamycin activates autophagy in human chondrocytes preventing the development of osteoarthritis (OA) like changes in vitro, while the systemic injection of rapamycin reduces the severity of experimental osteoarthritis in a murine model of OA in vivo. Since the systemic use of rapamycin is associated with numerous side effects, the goal of the current study was to examine the beneficial effect of local intra-articular injection of rapamycin in a murine model of OA and to elucidate the mechanism of action of rapamycin on articular cartilage. Methods: Destabilization of the medial meniscus (DMM) was performed on 10-week-old male mice to induce OA. Intra-articular injections of 10 μl of rapamycin (10 μM) were administered twice weekly for 8 weeks. Articular cartilage damage was analyzed by histology using a semi-quantitative scoring system at 8 and 12 weeks after surgery. Mammalian target of rapamycin (mTOR), light chain 3 (LC3), vascular endothelial growth factor (VEGF), collagen, type X alpha 1 (COL10A1), and matrix metallopeptidase 13 (MMP13) expressions were analyzed by immunohistochemistry. VEGF, COL10A1, and MMP13 expressions were further examined via quantitative RT-PCR (qPCR). Results: Intra-articular injection of rapamycin significantly reduced the severity of articular cartilage degradation at 8 and 12 weeks after DMM surgery. A reduction in mTOR expression and the activation of LC3 (an autophagy marker) in the chondrocytes was observed in the rapamycin treated mice. Rapamycin treatment also reduced VEGF, COL10A1, and MMP13 expressions at 8 and 12 weeks after DMM surgery. Conclusion: These results demonstrate that the intra-articular injection of rapamycin could reduce mTOR expression, leading to a delay in articular cartilage degradation in our OA murine model. Our observations suggest that local intra-articular injection of rapamycin could represent a potential therapeutic approach to prevent OA.
Background: The management of soft tissue balance during surgery is essential for the success of total knee arthroplasty (TKA) but remains difficult, leaving it much to the surgeon’s feel. Previous assessments for soft tissue balance have been performed under unphysiological joint conditions, with patellar eversion and without the prosthesis only at extension and 90 deg of flexion. We therefore developed a new tensor for TKA procedures, enabling soft tissue balance assessment throughout the range of motion while reproducing postoperative joint alignment with the patellofemoral (PF) joint reduced and the tibiofemoral joint aligned. Our purpose in the present study was to clarify joint gap kinematics using the tensor with the CT-free computer assisted navigation system. Method of Approach: Joint gap kinematics, defined as joint gap change during knee motion, was evaluated during 30 consecutive, primary posterior-stabilized (PS) TKA with the navigation system in 30 osteoarthritic patients. Measurements were performed using a newly developed tensor, which enabled the measurement of the joint gap throughout the range of motion, including the joint conditions relevant after TKA with PF joint reduced and trial femoral component in place. Joint gap was assessed by the tensor at full extension, 5 deg, 10 deg, 15 deg, 30 deg, 45 deg, 60 deg, 90 deg, and 135 deg of flexion with the patella both everted and reduced. The navigation system was used to obtain the accuracy of implantations and to measure an accurate flexion angle of the knee during the intraoperative joint gap measurement. Results: Results showed that the joint gap varied depending on the knee flexion angle. Joint gap showed an accelerated decrease during full knee extension. With the PF joint everted, the joint gap increased throughout knee flexion. In contrast, the joint gap with the PF joint reduced increased with knee flexion but decreased after 60 deg of flexion. Conclusions: We clarified the characteristics of joint gap kinematics in PS TKA under physiological and reproducible joint conditions. Our findings can provide useful information for prosthetic design and selection and allow evaluation of surgical technique throughout the range of knee motion that may lead to consistent clinical outcomes after TKA.
We conducted a prospective randomised study of anatomical single-bundle (A-SB group) versus double-bundle (A-DB group) anterior cruciate ligament (ACL) reconstruction using the hamstrings tendons. Twenty patients with unilateral ACL deficiency were randomised into two groups. We created the bone tunnels at the position of the original insertion of the anteromedial bundle footprint and posterolateral bundle footprint in the A-DB group and at the central position between these two bundles in the A-SB group. All of the patients were tested before ACL reconstruction and one year after surgery. The KT-1000 measurements, isokinetic muscle peak torque and heel-height difference were evaluated and the general knee condition was assessed by Lysholm score. For pre- and postoperative stability assessment, we used the six-degrees-of-freedom of knee kinematic measurement system using an electromagnetic device (the EMS) for quantitative assessment during the Lachman test and the pivot shift test. There were no significant differences in the KT-1000 measurements, isokinetic muscle peak torque, heel-height difference, and Lysholm score at one-year follow-up between these two groups. The EMS data showed there were significant differences in the acceleration of the pivot shift test between the operated knee and the contralateral normal knees in the A-SB group. In conclusion, clinical outcomes were equally good in both groups. However, the EMS data showed the anatomical double-bundle ACL reconstruction tended to be biomechanically superior to the single-bundle reconstruction.