Nobutake Ozeki

Meniscotibial ligament dysfunction has been proposed as a factor contributing to medial meniscus extrusion (MME), a key feature of medial knee OA. This study investigated meniscotibial ligament pockets, defined as fluid-equivalent signals on MRI, as MRI findings that may reflect changes at the meniscotibial ligament insertion, including possible detachment. We examined their prevalence across Kellgren–Lawrence (KL) grades and their anatomical distribution. Participants from the Kanagawa Knee Study without lateral knee OA underwent spoiled gradient–recalled MRI. The “pocket sign,” defined as a fluid-equivalent signal between the medial tibial cortex and the ligament attachment on axial and coronal images, was used as an MRI finding potentially related to meniscotibial ligament detachment. Multivariable logistic regression evaluated associations between pocket presence and clinical factors. Pocket location was classified relative to the medial collateral ligament (MCL). A subset underwent surgical assessment during knee arthroplasty. Pocket prevalence increased with KL grade, from 40% in KL grade 0 to 100% in KL grade 4. Higher KL grade was independently associated with pocket presence (OR 2.56 per grade increase, p < 0.001). Age showed a limited and inconsistent association, whereas sex and BMI were not associated. In KL grade 0 knees, pockets were predominantly located anterior to the MCL and were associated with mild MME. Surgical findings supported the MRI results. Meniscotibial ligament pockets are present even in KL grade 0 knees and become more frequent with increasing radiographic severity. Their anterior predominance relative to the MCL suggests a characteristic distribution pattern. The pocket sign may serve as an MRI marker of meniscotibial ligament status.

Background Synovial mesenchymal stem cells (MSCs) are promising for cartilage regeneration; however, freeze–thaw injury during cryopreservation impairs their proliferative capacity and may limit therapeutic efficacy. Glutathione, a key intracellular antioxidant, maintains redox homeostasis during cellular stress. Although redox modulation has been shown to improve cryopreservation outcomes in other stem cell types, its effectiveness in synovial MSCs remains unclear. This study aimed to determine whether cysteine preconditioning improves the proliferative capacity of synovial MSCs after freeze-thawing and to investigate the association between cysteine-induced glutathione responsiveness and donor-dependent variability in cryopreservation outcomes. Methods Human synovial MSCs were isolated from synovial tissue obtained from six patients with osteoarthritis undergoing total knee arthroplasty. MSCs were cultured with or without 1 mM L-cysteine for one week prior to cryopreservation. After freeze–thawing, proliferative capacity, colony-forming ability, and chondrogenic differentiation potential were assessed using multiple samples (six samples) from each donor. Intracellular glutathione (GSH) levels were quantified using fluorescence-based assays, and donor-matched analyses were performed to examine correlations between cysteine-induced GSH responsiveness and post–freeze–thaw changes in cell number and colony formation. Results Freeze–thaw without cysteine supplementation consistently reduced cell numbers and colony formation compared with fresh MSCs across all donors. In contrast, cysteine preconditioning before cryopreservation increased post–freeze–thaw cell numbers and colony counts in all donors, although the magnitude of recovery varied among individuals. Chondrogenic differentiation capacity after freeze–thaw was largely preserved, and cysteine preconditioning did not adversely affect chondrogenic outcomes. Cysteine preconditioning significantly increased intracellular glutathione (GSH) levels in all six donors. Donor-matched analyses demonstrated strong positive correlations between cysteine-induced GSH responsiveness and post–freeze–thaw changes in cell numbers (r = 0.95) and colony counts (r = 0.91). Conclusions Cysteine preconditioning improved the proliferative capacity of synovial MSCs after freeze-thawing without impairing chondrogenic differentiation. Strong associations between cysteine-induced glutathione responsiveness and recovery of cell number and colony formation after freeze-thawing indicate that donor-dependent differences contribute to variability in cryopreservation outcomes. These findings suggest that targeting glutathione-related redox pathways may represent a useful strategy for optimizing the cryopreservation of synovial MSCs.

Background: Medial meniscal extrusion (MME) contributes to knee osteoarthritis and is often caused by a medial meniscal posterior root tear (MMPRT). Although early surgical repair of MMPRT improves outcomes, MME often persists. Centralization techniques aim to reduce meniscal extrusion by anchoring the capsule to the tibial plateau; however, their clinical effectiveness when combined with MMPRT repair remains uncertain. Purpose: To evaluate the efficacy of centralization combined with MMPRT repair in reducing MME using intraoperative ultrasound. Study Design: Case series; Level of evidence, 4. Methods: The study included 26 patients who underwent MMPRT repair with a pullout technique and centralization with three knotless anchors. Of these, 22 patients also underwent additional high tibial osteotomy. Initial tensions of 0 to 40 N were applied to the pullout repair sutures at 60° of knee flexion, and MME was measured by intraoperative ultrasound. MME was also measured at 0°, 30°, 60°, 90°, and 120° of knee flexion, as well as at internally and externally rotated positions (IR and ER) at 30° and 90° of knee flexion, before MMPRT repair, after repair, and after centralization. A total of 22 patients underwent additional high tibial osteotomy after MMPRT repair and centralization. Results: When tension of 0 to 40 N was applied to the pullout repair sutures at 60°, the median MME decreased with increasing tension, with a significant reduction observed at 30 and 40 N compared with lower tension levels. Moreover, at tensions ≥30 N, the median MME remained P < .001) and also smaller than after repair ( P < .006). At 120°, MME after centralization was significantly smaller than before repair ( P < .001), and the difference among the 3 conditions was also significant ( P = .03). Centralization resulted in the smallest MME at both flexion angles. The median MME before MMPRT repair, after repair, and after centralization at 30° were all smaller in the MME in the ER position. Conversely, the ER-IR differences were slight at 90°. Conclusion: Intraoperative ultrasound demonstrated that MMPRT repair reduced MME compared with the preoperative condition, and the addition of centralization further enhanced this reduction, yielding greater improvement than MMPRT repair alone.

Background: Mesenchymal stem cell (MSC) therapy has emerged as a promising treatment option for knee osteoarthritis. Adipose MSCs are commonly used due to their easy accessibility; however, synovial MSCs have demonstrated a superior capacity for cartilage matrix synthesis. The mechanism underlying this difference in therapeutic efficacy may involve lubricin, a crucial glycoprotein that maintains joint lubrication and protects cartilage. Notably, lubricin levels decrease during the progression of osteoarthritis. The aim of this study was to compare extracellular lubricin secretion by human synovial MSCs versus adipose MSCs. We also analyzed potential correlations between synovial MSC lubricin secretion and synovial inflammation. Methods: Tissues for MSC isolation were obtained from 16 human donors with osteoarthritis who underwent total knee arthroplasty. Synovium was collected from the suprapatellar pouch on the femoral side, whereas adipose tissue was harvested from the subcutaneous layer of the knee skin incision. The synovial and adipose MSCs from each donor were cultured for 48 h (six replicate wells per donor), and lubricin concentrations in culture supernatants were measured using ELISA. For 11 donors, lubricin concentrations were measured directly, whereas the concentrations were normalized to cell number for the other 5 donors. MSC identity was assessed by flow cytometry and trilineage differentiation assays. Correlations between synovial MSC lubricin secretion and clinical parameters, including age, CRP, WBC, numerical rating scale for knee pain, synovial redness, synovial hyperplasia, and Krenn’s synovitis score, were assessed. Results: Lubricin secretion was significantly greater from synovial MSCs than from adipose MSCs in 8 of the 11 directly analyzed MSC supernatants (p = 0.014 by Wilcoxon matched-pairs signed-rank test). However, the results from all 5 donors whose lubricin concentrations were normalized to cell number revealed a consistently higher lubricin secretion by synovial MSCs than by adipose MSCs. Every representative preparation of synovial and adipose MSCs fulfilled standard MSC identity criteria. No correlations were found between lubricin secretion and synovial inflammation or any clinical parameters. Conclusions: More lubricin was secreted from human synovial MSCs than from adipose MSCs in the majority of donors examined. These findings support the potential therapeutic advantages of using synovial MSCs for osteoarthritis treatment.