Disease-Modifying Effects of Lenvatinib, a Multiple Receptor Tyrosine Kinase Inhibitor, on Posttraumatic Osteoarthritis of the Knee.

Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.

MPFL Reconstruction Combined with a Modified Elmslie-Trillat Procedure for Recurrent Patellofemoral Instability.

Several combined procedures have been reported for treating recurrent patellofemoral instability (RPI) with various types and severity of morphological abnormalities, but none have identified absolute threshold values as indications for surgery. We performed medial patellofemoral ligament (MPFL) reconstruction combined with a modified Elmslie-Trillat (ET) procedure on 24 knees (10 male and 11 female patients) to treat RPI with morphological abnormalities corresponding to elevated tibial tubercle-trochlear groove (TT-TG) distance, significant patella alta, and trochlear dysplasia. The inclusion criteria were RPI with morphological abnormalities corresponding to one or more of the following: sulcus angle > 160 degrees, trochlear dysplasia of Dejour classification C or D, Caton-Deschamps index > 1.5, lateral shift ratio > 50%, congruence angle > 15 degrees, or TT-TG distance > 20 mm, including habitual dislocation of the patella. Skeletally immature patients and those with congenital dislocation of the patella were excluded. The Kujala score, International Knee Documentation Committee subjective score, Knee Injury and Osteoarthritis Outcome score (KOOS), and each item of the KOOS improved significantly after surgery. Patellar apprehension sign was present preoperatively in all cases, but all disappeared postoperatively. No instance of postoperative redislocation was observed. On radiographic examination, the mean Q angle, tilting angle, lateral shift ratio, congruence angle, Caton-Deschamps index, Insall-Salvati index, and TT-TG distance improved significantly after surgery. There were no significant differences in sulcus angle after surgery. These results suggest MPFL reconstruction combined with a modified ET procedure provides satisfactory outcomes based on radiological and clinical evaluations for RPI with morphological abnormalities corresponding to elevated TT-TG distance, significant patella alta, and trochlear dysplasia.

Analysis of the running position of the popliteal artery and branching level of the anterior tibial artery detected by magnetic resonance imaging to avoid vessel injury during surgery around the knee joint.

Background: Vessel injuries during total knee arthroplasty or high tibial osteotomy are rare but have serious complications. This study aimed to analyze the running position of the popliteal artery (PA) and branching level of the anterior tibial artery (ATA), using magnetic resonance imaging (MRI). This analysis might be helpful in avoiding unnecessary vessel injury. Methods: In total, 105 patients (41 men and 64 women), whose running position of the PA and branching level of the ATA could be detected by preoperative MRI, were included in this study. We configured zones A, B, C, and D to be 5-10, 15-20, 25-30 and 35-40 mm distal from the lateral tibial plateau in the axial view, respectively. First, the distance between the posterior cortex of the tibia and anterior border of the PA was measured. Second, the PA position from the medial border of the tibia was measured. This measured value was divided by the transverse diameter of the tibia, and multiplied by 100 to obtain the PA position from the medial border of the tibia. Third, the branching level of ATA was measured from the joint line. Subsequently, each value was compared between men (the M group) and women (the W group). Results: The distance between the posterior cortex of the tibia and the anterior border of the PA was 5.5 ± 1.9, 10.4 ± 2.4, 12.5 ± 2.3 and 12.5 ± 2.3 (mm; mean ± SD) in zones A, B, C, and D, respectively. Comparing both groups, this distance was significantly larger (more separated posteriorly) in zones C and D in the M group. The PA position from the medial border of the tibia was 51.7 ± 6.5, 52.7 ± 8.2, 56.7 ± 10.5 and 66.8 ± 14 (%; mean ± SD) in zones A, B, C, and D, respectively. On comparing the two groups, this position was significantly larger (more laterally shifted) in zone D in the W group. The branching level of the ATA was not detected within 40 mm distal to the joint line in 92 patients (87.6%). However, it was detected within 40 mm (mean 32.5 mm; range 20-38) in 12 patients (11.4%). Among them, 11 were women. Only one woman had an aberrant branching pattern: the ATA bifurcated at the joint level. Conclusion: The PA positioned closest at the joint level, gradually separated and shifted laterally towards the distal side. The distance between the posterior cortex of the tibia and the anterior border of the PA was closer in women than in men in zones C and D. Although a difference of 2 mm is small, the risk of PA injury can be considered to be higher in women than in men. Furthermore, ATA injury is also a concern during retraction of the tibialis anterior muscle posteriorly, and the descending cut of the tibial tuberosity, particularly in women.

Regenerative effects of human chondrocyte sheets in a xenogeneic transplantation model using immune-deficient rats.

Although cell transplantation has attracted much attention in regenerative medicine, animal models continue to be used in translational research to evaluate safety and efficacy because cell sources and transplantation modalities are so diverse. In the present study, we investigated the regenerative effects of human chondrocyte sheets on articular cartilage in a xenogeneic transplantation model using immune-deficient rats. Osteochondral defects were created in the knee joints of immune-deficient rats that were treated as Group A, untreated (without transplantation); Group B, transplantation of a layered chondrocyte sheet containing 5.0 × 105 cells (layered chondrocyte sheet transplantation); Group C, transplantation of a synoviocyte sheet containing 5.0 × 105 cells (synoviocyte sheet transplantation); or Group D, transplantation of both a synoviocyte sheet plus a layered chondrocyte sheet, each containing 5.0 × 105 cells (synoviocyte sheet plus layered chondrocyte sheet transplantation). Histological evaluation demonstrated that Group B showed cartilage regeneration with hyaline cartilage and fibrocartilage. In Groups C and D, the defect was filled with fibrous tissue but no hyaline cartilage. Transplanted cells were detected at 4 and 12 weeks after transplantation, but the number of cells had decreased at 12 weeks. Our results indicate that layered chondrocyte sheet transplantation contributes to articular cartilage regeneration; this model proved useful for evaluating these regenerative effects.