Background. Meniscus repair can restore the function of torn meniscus in anterior cruciate ligament (ACL)-reconstructed knees. However, few reports investigate the relationship between concurrent meniscus repair with ACL reconstruction and postoperative meniscal position. This study aimed to evaluate the size of the medial meniscus in patients who underwent ACL reconstruction and concomitant all-inside medial meniscus repair. Methods. This study received the approval of our Institutional Review Board. Twenty patients underwent ACL reconstruction and concurrent medial meniscus repair of a peripheral longitudinal tear using the FasT-Fix meniscal repair device. Medial tibial plateau length (MTPL) and width (MTPW) were determined by radiographic images. We evaluated the Lysholm score, anteroposterior instability (difference in KT-2000 arthrometer measurement), meniscal healing, and magnetic resonance imaging (MRI)-based medial meniscal length (MML) and width (MMW). The healing status of repaired medial meniscus was assessed by 2nd-look arthroscopy. Results. ACL reconstruction improved the Lysholm score and anteroposterior instability. All the patients showed complete healing of the repaired meniscus in 2nd-look arthroscopic evaluation. Significant increase of MML and MML percentage (100 × MML/MTPL) was observed after concurrent all-inside medial meniscus repair with ACL reconstruction. However, MMW and MMW percentage (100 × MMW/MTPW) were not affected. Conclusions. Concurrent all-inside medial meniscus repair with ACL reconstruction had satisfactory clinical results. Anteroposterior length of the medial meniscus increased after surgery. Our results suggest that medial meniscus repair associated with ACL reconstruction may affect the biomechanical function of the medial meniscus. Level of Evidence. Case-control study, Level IV. Disclosure. The authors have no conflicts of interest

Summary. Our statistical shape analysis showed that size is the primary geometrical variation factor in the medial meniscus. Shape variations are primarily focused in the posterior horn, suggesting that these variations could influence cartilage contact pressures. Introduction. Variations in meniscal geometry are known to influence stresses and strains inside the meniscus and the articulating cartilage surfaces. This geometry-dependent functioning emphasizes that understanding the natural variation in meniscus geometry is essential for a correct selection of allograft menisci and even more crucial for the definition of different sizes for synthetic meniscal implants. Moreover, the design of such implants requires a description of 3D meniscus geometry. Therefore, the aim of this study was to quantify 3D meniscus geometry and to determine whether variation in medial meniscus geometry is size or shape driven. Patients & Methods. Sagittal knee MR images (n=35; 15 males, 20 females, aged 33±12) were acquired at 3 Tesla using a 3D SPACE sequence with isotropic resolution of 0.5×0.5×0.5mm. 3D models were generated by manual segmentation of the medial menisci from the MR scans. The surface of a reference meniscus was then described by 250 landmarks. Using an affine iterative closest point transformation, these landmarks were registered onto the full set of 3D models. Based on the set of corresponding landmarks, a point distribution model was created using the Shapeworks software (NITRC, University of Utah), an open source algorithm for constructing correspondence-based statistical models of sets of similar shapes. Several modules from Shapeworks and the Arthron software (UCD, Dublin) were used to perform principal component analysis (PCA) upon the set of landmarks. The results of the PCA enabled quantification and visualisation of the primary modes of variation in meniscal geometry. Results. The majority (77%) of variation in medial meniscus geometry was found to be due to sizing (principal component (PC) 1). Including the shape-related PC's 2 to 4, increased the cumulative percentage of represented geometry variation to over 90%. The independent shape variations described by PCs 2–4 all display larger variations in geometry of the posterior meniscal horn than the anterior section. Discussion. From this study, we can conclude that geometry variation of the medial meniscus is mainly determined by differences in size. However, since the posterior aspect of the medial meniscus experiences higher loads during daily activities than the anterior part, the shape variations described by PCs 2–4 may have a significant influence on cartilage contact pressures. Therefore, PCA alone does not provide sufficient information to define the number of implant sizes to cover a majority of the population. Analysis of the sensitivity of cartilage contact pressures to the shape variations identified in this analysis could provide the additional information needed

The aim of this work was to develop a novel, accessible and low-cost method, which is sufficient to measure changes in meniscal position in a whole-knee joint model performing dynamic motion in a knee simulator. An optical tracking method using motion markers, MATLAB (MATLAB, The MathWorks Inc.) and a miniature camera system (Raspberry Pi, UK) was developed. Method feasibility was assessed on porcine whole joint knee samples (n = 4) dissected and cemented to be used in the simulator (1). Markers were placed on three regions (medial, posterior, anterior) of the medial meniscus with corresponding reference markers on the tibial plateau, so the relative meniscal position could be calculated. The Leeds high kinematics gait profile scaled to the parameters of a pig (1, 2) was driven in displacement control at 0.5 Hz. Videos were recorded at cycle-3 and cycle-50. Conditions tested were the capsule retained (intact), capsule removed and a medial posterior root tear. Mean relative displacement values were taken at time-points relating to the peaks of the axial force and flexion-extension gait inputs, as well as the range between the maximum and minimum values. A one-way ANOVA followed by Tukey post hoc analysis were used to assess differences (p = 0.05). The method was able to measure relative meniscal displacement for all three meniscal regions. The medial region showed the greatest difference between the conditions. A significant increase (p < 0.05) for the root tear condition was found at 0.28s and 0.90s (axial load peaks) during cycle-3. Mean relative displacement for the root tear condition decreased by 0.29 mm between cycle-3 and cycle-50 at the 0.28s time-point. No statistically significant differences were found when ranges were compared at cycle-3 and cycle-50. The method was sensitive to measure a substantial difference in medial-lateral relative displacement between an intact and a torn state. Meniscus extrusion was detected for the root tear condition throughout test duration. Further work will progress onto human specimens and apply an intervention condition

Altered mechanical loading is a widely suggested, but poorly understood potential cause of cartilage degeneration in osteoarthritis. In rodents, osteoarthritis is induced following destabilization of the medial meniscus (DMM). This study estimates knee kinematics and contact forces in rats with DMM to gain better insight into the specific mechanisms underlying disease development in this widely-used model. Unilateral knee surgery was performed in adult male Sprague-Dawley rats (n=5 with DMM, n=5 with sham surgery). Radio-opaque beads were implanted on their femur and tibia. 8 weeks following knee surgery, rat gait was recorded using the 3D²YMOX setup (Sanctorum et al. 2019, simultaneous acquisition of biplanar XRay videos and ground reaction forces). 10 trials (1 per rat) were calibrated and processed in XMALab (Knörlein et al. 2016). Hindlimb bony landmarks were labeled on the XRay videos using transfer learning (Deeplabcut, Mathis et al. 2019; Laurence-Chasen et al. 2020). A generic OpenSim musculoskeletal model of the rat hindlimb (Johnson et al. 2008) was adapted to include a 3-degree-of-freedom knee. Inverse kinematics, inverse dynamics, static optimization of muscle forces, and joint reaction analysis were performed. In rats with DMM, knee adduction was lower compared to sham surgery. Ground reaction forces were less variable with DMM, resulting in less variability in joint external moments. The mediolateral ground reaction force was lower, resulting in lower hip adduction moment, thus less force was produced by the rectus femoris. Rats with DMM tended to break rather than propel, resulting in lower hip flexion moment, thus less force was produced by the semimembranosus. These results are consistent with lower knee contact forces in the anteroposterior and axial directions. These preliminary data indicate no overloading of the knee joint in rats with DMM, compared with sham surgery. We are currently expanding our workflow to finite element analysis, to examine mechanical cues in the cartilage of these rats (Fig1G)

The meniscus is a fibrocartilaginous tissue that plays an important role in controlling the complex biomechanics of the knee. Many histological and mechanical studies about meniscal attachment have been carried out, and medial meniscus (MM) root repair is recommended to prevent subsequent cartilage degeneration following MM posterior root tear. However, there are only few studies about the differences between meniscus root and horn cells. The goal of this study was to clarify the differences between these two cells. Tissue samples were obtained from the medial knee compartments of 10 patients with osteoarthritis who underwent total knee arthroplasty. Morphology, distribution, and proliferation of MM root and horn cells, as well as gene and protein expression levels of Sry-type HMG box (SOX) 9 and type II collagen (COL2A1) were determined after cyclic tensile strain (CTS) treatment. Horn cells had a triangular morphology, whereas root cells were fibroblast-like. The number of horn cells positive for SOX9 and COL2A1 was considerably higher than that of root cells. Although root and horn cells showed similar levels of proliferation after 48, 72, or 96 h of culture, more horn cells than root cells were lost following 2-h CTS (5% and 10% strain). SOX9 and COL2A1 mRNA expression levels were significantly enhanced in horn cells compared with those in root cells after 2- and 4-h CTS (5%) treatment. This study demonstrates that MM root and horn cells have distinct characteristics and show different cellular phenotypes. Our results suggest that physiological tensile strain is important for activating extracellular matrix production in horn cells. Restoring physiological mechanical stress may be useful for promoting healing of the MM posterior horn

Although osteoarthritis (OA) is characterized by articular cartilage damage, synovial inflammation is a prominent feature contributing to disease progression. In addition to synovial tissue resident macrophages, infiltrating macrophages and monocytes, their lineage precursors, may also contribute to pathological processes. In mice, peripheral blood monocytes may be categorized according to pro-inflammatory/classical and patrolling/non-classical subsets. The aim of this study was to identify profiles of peripheral blood monocyte subsets as well as different synovial macrophage phenotypes during disease development. OA was induced in knees of C57BL/6 mice by destabilization of the medial meniscus (DMM). Blood was harvested from the facial vein 7 days prior to and 1, 7, 14, 28, and 56 days post induction of OA. Separate mice were sham-operated as a control. Monocyte subsets and synovial macrophage populations were identified by flow cytometry. Levels of classical monocytes were significantly higher at day 14 (p<0.001) and day 28 (p=0.031) in peripheral blood of DMM-operated mice compared to control. Furthermore, the percentage of non-classical monocytes was significantly lower in DMM-mice at day 14 (p=0.026). At day 56 post OA-induction, an increase in total synovial macrophages (CD11b+F4/80+ cells) was observed between DMM and sham operated knees (p=0.021). The ratio between pro-inflammatory (CD11b+F4/80+CD86+) and tissue repair (CD11b+F4/80+CD206+) synovial macrophage subsets tended to be higher in DMM knees, however this finding was not statistically significant (p>0.05). In light of the present findings, further investigation is required to elucidate the relationship of peripheral blood monocyte subsets to synovial inflammation and features of OA pathogenesis

Introduction. Degenerative meniscal tears are the most common meniscal lesions, representing huge clinical and socio-economic burdens. Their role in knee osteoarthritis (OA) onset and progression is well established and demonstrated by several retrospective studies. Effective preventive measures and non-surgical treatments for degenerative meniscal lesions are still lacking, also because of the lack of specific and accurate animal models in which test them. Thus, we aim to develop and validate an accurate animal model of meniscus degeneration. Method. Three different surgical techniques to induce medial meniscus degenerative changes in ovine model were performed and compared. A total of 32 sheep (stifle joints) were subjected to either one of the following surgical procedures: a) direct arthroscopic mechanical meniscal injury; b) peripheral devascularization and denervation of medial meniscus; c) full thickness medial femoral condyle cartilage lesion. In all the 3 groups, the contralateral joint served as a control. Result. From a visual examination of the knee joint emerged a clear difference between control and operated groups, in the menisci but also in the cartilage, indicating the onset of OA-related cartilage degeneration. The meniscal and cartilaginous lesions were characterized by different severity and location in the different groups. For instance, a direct meniscal injury caused cartilaginous lesions especially in the medial part of the condyles, and the other approaches presented specific signature. Evaluation of scoring scales (e.g. ICRS score) allowed the quantification of the damage and the identification of differences among the four groups. Conclusion. We were effectively able to develop and validate a sheep model of meniscal degeneration which led to the onset of OA. This innovative model will allow to test in a pre-clinical relevant setting innovative approaches to prevent meniscal-related OA. Funding. Project PNRR-MAD-2022-12375978 funded by Italian Ministry of Health

Medial meniscus tear has been proposed as a potential etiology of spontaneous osteonecrosis of the knee (SONK). Disruption of collagen fibers within the meniscus causes meniscal extrusion, which results in alteration in load distribution in the knee. A recent study has demonstrated high incidence of medial meniscus extrusion in the knee with SONK. Our purpose was to determine whether the extent of medial meniscus extrusion correlates with the severity of SONK in the medial femoral condyle. Anteroposterior and lateral knee radiographs were taken with the patients standing. Limb alignment was expressed as the femorotibial angle (FTA) obtained from the anteroposterior radiograph. The stage of progression of SONK was determined according to the radiological classification system described by Koshino. After measurement of anteroposterior, mediolateral, and superoinferior dimensions of the hypointense T1 signal intensity lesion of MRI, its ellipsoid volume was calculated with the three dimensions. Meniscal pathology (degeneration, tear, and extrusion) were also evaluated by MRI. Of the 18 knees with SONK, we found 5 knees at the radiological stage 2 lesions, 9 knees at the stage 3, and 4 knees at the stage 4. Whereas the ellipsoid volume of SONK lesion significantly increased with the stage progression, the volume was significantly greater at stage 4 than stage 2 or 3. All the 18 knees with SONK in the present study showed substantial extrusion (> 3mm) and degeneration of the medial meniscus. While medial meniscal extrusion increased with the stage progression, medial meniscus was significantly extruded at stage 3 or 4 compared with stage 2. A significant increase in FTA was found with the stage progression. FTA was significantly greater at stage 4 than stage 2 or 3. Multiple linear regression analysis revealed that medial meniscus extrusion and FTA were useful predictors of the volume of SONK lesion. This study has clearly shown a significant correlation between the extent of medial meniscus extrusion and the stage and volume of SONK lesion. Degeneration and tears of the medial meniscus in combination with extrusion may result in loss of hoop stress distribution in the medial compartment, which could increase the load in the medial femoral condyle. In addition to meniscal pathology, knee alignment can influence load distribution in the medial compartment biomechanically. Multiple linear regression analysis indicates that an increase in FTA concomitant with a greater extrusion of medial meniscus could result in greater lesion and advanced radiological stage of SONK. Taken together, alteration in compressive force transmission through the medial compartment by meniscus extrusion and varus alignment could develop subchondral insufficiency fractures in the medial femoral condyle, which is considered to be one of the main contributing factors to SONK development. There was high association of medial meniscus extrusion and FTA with the radiological stage and volume of SONK lesion. Increased loading in the medial femoral condyle with greater extrusion of medial meniscus and varus alignment may contribute to expansion and secondary osteoarthritic changes of SONK lesion

Recent findings have identified the importance of previously undiagnosed or neglected meniscus lesions in association with anterior cruciate ligament (ACL) injuries (e.g. medial meniscus ramp lesions and posterior root tears of the lateral meniscus). There is increasing biomechanical evidence that they bear the potential to alter both anteroposterior and rotational laxity patterns in ACL injured knees. Few data exist with respect to the presence of these specific tear entities in large series of ACL injured patients. The purpose of the study was to analyze the meniscus tear pattern in a series of ACL injured knees with a special focus on ramp lesions of the medial meniscus and posterior root lesions of the lateral meniscus. The hypothesis was that a significant number of ACL injured patients would display these types of lesions. Data from 358 patients undergoing an ACL reconstruction (227 males /131 females, age: 28±10) were extracted from a center-based registry. The type of ACL tear (partial versus complete) as well as the presence of associated meniscus lesions were documented. Meniscus lesions were classified into the following categories: medial ramp lesions, lateral root lesions, medial ramp and lateral root lesion, other medial meniscus injuries, other lateral meniscus injuries, other bimeniscal injuries. Chi-square tests were used to determine whether the percentage of meniscal lesions differed between types of ACL tear, gender and age (below 21, 21–35, above 35). Significance was set at p < 0.05. Isolated ACL tears were present in 107 (30%) of the operated knees (31 partial; 327 complete). Complete ACL lesions were more likely to present an associated meniscus injury (321 out of 327, 71%) than partial tears (13 out of 31, 42%). The incidence of meniscus injuries which are associated with ACL tears is very high (70%). Previously undiagnosed or neglected meniscus injuries like medial ramp or lateral root tears could be identified in 35% of patients. As such, the hypothesis was confirmed that an important amount of ACL injured knees display this specific intraarticular soft tissue damage. A systematic evaluation of these lesions under arthroscopy should thus be performed and specific repair needs to be evaluated

Chondrocytic activity is downregulated by compromised autophagy and mitochondrial dysfunction to accelerate the development of osteoarthritis (OA). Irisin is a cleaved form of fibronectin type III domain containing 5 (FNDC5) and known to regulate bone turnover and muscle homeostasis. However, little is known about the role of irisin in chondrocytes and the development of OA. This talk will shed light on FNDC5 expression by human articular chondrocytes and compare normal and osteoarthritic cells with respect to autophagosome marker LC3-II and oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG). In chondrocytes in vitro, irisin improves IL-1β-mediated growth inhibition, loss of specific cartilage markers and glycosaminoglycan production. Irisin further suppressed Sirt3 and UCP- 1 to improve mitochondrial membrane potential, ATP production, and catalase. This attenuated IL-1β-mediated production of reactive oxygen species, mitochondrial fusion, mitophagy, and autophagosome formation. In a surgical murine model of destabilization of the medial meniscus (DMM) intra-articular administration of irisin alleviates symptoms like cartilage erosion and synovitis. Furthermore, gait profiles of the treated limbs improved. In chondrocytes, irisin treatment upregulates autophagy, 8-OHdG and apoptosis in cartilage of DMM limbs. Loss of FNDC5 in chondrocytes correlates with human knee OA and irisin repressed inflammation-mediated oxidative stress and deficient extracellular matrix synthesis through retaining mitochondrial biogenesis and autophagy. The talk sheds new light on the chondroprotective actions of this myokine and highlights the remedial effects of irisin during progression of OA

Abstract. Introduction. The medial meniscus is crescent shaped and it is wider posteriorly than anteriorly. It covers up to 60 % of the articular surface of medial tibial condyle and helps with the loading distribution in the medial compartment. Meniscal lesions occur in association with ACL tears in 60 % of the time. The posterior aspect of the menisco-capsular junction is known as the meniscal rampzone. If not addressed during surgery, it could lead to unfavourable results. Objective. Incidence of ramp lesion following ACL injuries. Methods. Observational study of 100 patients at EL Hadara Main University Hospital who underwent anterior cruciate ligament reconstruction. MRI and arthroscopic diagnosis was done to detect Ramp lesions associated with ACL ruptures in November 2017 till November 2019. Results. Incidence was 9%. Duration of injury and increased medial meniscal slope were associated with increased incidence of ramp lesion. MRI signs were present in 79% of cases without Ramp lesion, 100% in Cases with ramp lesion. Mode of Injury and presence of locking or giving way symptoms were not associated with increased incidence. Conclusion. The ramp lesion at the posterior aspect of the meniscus is difficult to visualize from standard anterior portals and is, therefore, frequently missed and can be underestimated. Also, there are no specific MRI signs of this lesion. The overall incidence of ramp lesions in 100 cases that had undergone ACL reconstruction in our study was 9 %. It was found also that the longer the duration from injury, the more likely ramp lesion would occur. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

A comprehensive understanding of the self-repair abilities of menisci and their overall function in the knee joint requires three-dimensional information. However, previous investigations of the meniscal blood supply have been limited to two-dimensional imaging methods, which fail to accurately capture tissue complexity. In this study, micro-CT was used to analyse the 3D microvascular structure of the meniscus, providing a detailed visualization and precise quantification of the vascular network. A contrast agent (μAngiofil®) was injected directly into the femoral artery of cadaver legs to provide the proper contrast enhancement. First, the entire knee joint was analysed with micro-CT, then to increase the applicable resolution the lateral and medial menisci were excised and investigated with a maximum resolution of up to 4 μm. The resulting micro-CT datasets were analysed both qualitatively and quantitatively. Key parameters of the vascular network, such as vascular volume fraction, vessel radius, vessel length density, and tortuosity, were separately determined for the lateral and medial meniscus, and their four circumferential zones defined by Cooper. In accordance with previous literature, the quantitative micro-CT data confirm a decrease in vascular volume fraction along the meniscal zones. The highest concentration of blood vessels was measured in the meniscocapsular region 0, which is characterized by vascular segments with a significantly larger average radius. Furthermore, the highest vessel length density observed in zone 0 suggests a more rapid delivery of oxygen and nutrients compared to other regions. Vascular tortuosity was detected in all circumferential regions, indicating the occurrence of vascular remodelling in all tissue areas. In conclusion, micro-CT is a non-invasive imaging technique that allows for the visualization of the internal structure of an object in three dimensions. These advanced 3D vascular analyses have the potential to establish new surgical approaches that rely on the healing potential of specific areas of the meniscus. Acknowledgements: The authors acknowledge R. Hlushchuk, S. Halm, and O. Khoma from the University of Bern for their help with contrast agent perfusions

Osteoarthritis (OA) affects the whole joint and leads to chronic pain. The sympathetic nervous system (SNS) seems to be involved in OA pathogenesis, as indicated by in vitro studies as well as by our latest work demonstrating that sympathectomy in mice results in increased subchondral bone volume in the OA knee joint. We assume that chronic stress may lead to opposite effects, such as an increased bone loss in OA due to an elevated sympathetic tone. Therefore, we analyzed experimental OA progression in mice exposed to chronic stress. OA was induced in male C57BL/6J mice by surgical destabilization of the medial meniscus (DMM) and Sham as well as non-operated mice served as controls. Half of these groups were exposed to chronic unpredictable mild stress (CUMS). After 12 weeks, chronic stress efficiency was assessed using behavioral tests. In addition to measuring body weight and length, changes in subchondral bone were analyzed by μCT. Dynamic Weight Bearing system was used to monitor OA-related pain. Histological scoring will be conducted to investigate the severity cartilage degeneration and synovial inflammation. CUMS resulted in increased anxiety and significant decrease in body weight gain in all CUMS groups compared to non-CUMS groups. CUMS also increased serum corticosterone in healthy mice, with even higher levels in CUMS mice after DMM surgery. CUMS had no significant effect on subchondral bone, but subarticular bone mineral density and trabecular thickness were increased. Moreover, CUMS resulted in significant potentiation of DMM-associated pain. Our results suggest that the autonomic imbalance with increased sympathetic nervous activity induced by chronic stress exacerbates the severity of OA pain perception. We expect significantly increased cartilage degeneration as well as more severe synovial inflammation in CUMS DMM mice compared to DMM mice

No proven long-term joint-preserving treatment options exist for patients with irreparable meniscal damage. This study aimed to assess gait kinematics and contact pressures of novel fibre-matrix reinforced polyvinyl alcohol-polyethylene glycol (PVA-PEG) hydrogel meniscus implanted ovine stifle joints against intact stifles in a gait simulator. The gait simulator controlled femoral flexion-extension and applied a 980N axial contact force to the distal end of the tibia, whose movement was guided by the joint natural ligaments (Bartolo; ORS 2021;p1657- LB). Five right stifle joints from sheep aged >2 years were implanted with a PVA-PEG total medial meniscus replacement, fixed to the tibia via transosseous tunnels and interference screws. Implanted stifle joint contact pressures and kinematics in the simulator were recorded and compared to the intact group. Contact pressures on the medial and lateral condyles were measured at 55° flexion using Fujifilm Prescale Low Pressure film inserted under the menisci. 3D kinematics were measured across two 30 second captures using the Optotrak Certus motion-tracking system (Northern Digital Inc.). Medial peak pressures were not significantly different between the implanted and intact groups (p>0.4), while lateral peak pressures were significantly higher in the implanted group (p<0.01). Implanted stifle joint kinematics in the simulator did not differ significantly from the intact baseline (p>0.01), except for in distraction-compression (p<0.01). Our findings show that the fibre-matrix reinforced PVA-PEG hydrogel meniscal replacement restored the medial peak contact pressures. Similar to published literature (Fischenich; ABE 2018;46(11):1–12), the lateral peak pressures in the implanted group were higher than the intact. Joint kinematics were similar across groups, with slightly increased internal-external rotation in the implanted group. These findings highlight the effectiveness of the proposed approach and motivate future work on the development of a total meniscal replacement

Validation of a new meniscal root repair technique that will be biomechanically superior to current gold standard procedures and, at the same time, will allow controlled adjustable fixation. Medial and lateral meniscus from 10 porcine knees were collected. An iatrogenic posterior root tear was created and a single transosseous tibial tunnel technique that closely replicates the repair procedure with a 2-mm-wide-knottable braided tape was performed. Randomly, in one group (A) two simple cinch stitch were applied to suture the posterior root of the meniscus and, in the other group (B), a simple stich that holds the meniscus in two points in a crosse match configuration was used. For final fixation, alternating surgeon's knots (A group) and a doubled suture knot that allows an adjustable fixation were used (B group). All repairs were standardized for location and the repair stiches were placed in the body of the meniscus. The new suture configuration (B group) showed a better biomechanical performance in terms of load for both the medial [151,0-560,3] 306,9±173,8N and the lateral posterior root fixation [268,2-463,1] 347,4±74,3N in comparison to the cinch stitch (A group) [219,0-365,2] 268,9±58,7N and [219,0-413,6] 318,0±72N. The maximum stiffness was also higher for the new tested suture configuration (B group) for both the medial meniscus [10,6-34,5] 18,9±9,2N/mm vs [7,1-12,7] 10,9±2,2N/mm and the lateral meniscus [16,0-27,9] 21,6±5,5N/mm vs [7,6-15,6] 12,6±3,5N/mm. The presented new meniscal root repair is biomechanically superior to current gold standard techniques, as the cinch stich made with tape, keeping the simplicity and reproducibility of the procedure and, at the same time, is economically advantageous since a single tape in needed and allows adjustable fixation of the repair over a button

Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA. Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CRE. ERT2. ;Piezo1. fl/fl. Piezo2. fl/fl. ) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria. Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology. Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice

Introduction. Osteoarthritis (OA) is a chronic degenerative disease of the entire joint leading to joint stiffness and pain (PMID:33571663). Recent evidence suggests that the sympathetic nervous system (SNS) plays a role in the pathogenesis of OA (PMID:34864169). A typical cause for long-term hyperactivity of the SNS is chronic stress. To study the contribution of increased sympathetic activity, we analyzed the progression of OA in chronically stressed mice. Method. We induced OA in male C57BL/6J mice by destabilizing the medial meniscus (DMM)(PMID:17470400) and exposed half of these mice to chronic unpredictable mild stress (CUMS)(PMID:28808696). Control groups consisted of sham-operated mice with and without CUMS exposure. After 12 weeks, CUMS efficacy was determined by assessing changes in body weight gain and activity of mice, measuring splenic norepinephrine and serum corticosterone levels. OA progression was studied by histological analysis of cartilage degeneration and synovitis, and by μCT to evaluate changes in calcified cartilage and subchondral bone microarchitecture. A dynamic weight-bearing system was used to assess OA-related pain. Result. CUMS resulted in significantly decreased body weight gain and activity, as well as increased splenic norepinephrine and serum corticosterone concentrations compared to the respective controls. Surprisingly, already DMM alone resulted in elevated stress hormone levels. CUMS significantly exacerbated cartilage degeneration and synovial inflammation and increased OA pain in DMM mice. The underlying cellular and molecular mechanisms are currently being analyzed using FACS, single cell RNAseq, and spatial proteomics. Conclusion. Overall, chronic stress exacerbates OA severity and pain. Moreover, increased levels of stress hormones were observed in OA mice without CUMS induction, suggesting a complex bi-directional interaction between the SNS and OA. Targeting the autonomic nervous system, such as attenuating the SNS but also stimulating the activity of the parasympathetic nervous system, as a counterpart of the SNS, may therefore be promising for novel preventive or causal treatments of OA

Introduction. Osteoarthritis (OA) causes pain, stiffness, and loss of function due to degenerative changes in joint cartilage and bone. In some forms of OA, exercise can alleviate symptoms by improving joint mobility and stability. However, excessive training after joint injury may have negative consequences for OA development. Sensory nerve fibers in joints release neuropeptides like alpha-calcitonin gene-related peptide (alpha-CGRP), potentially affecting OA progression. This study investigates the role of alpha-CGRP in OA pathogenesis under different exercise regimen in mice. Method. OA was induced in C57Bl/6J WT mice and alpha-CGRP KO mice via surgical destabilization of the medial meniscus (DMM) at 12 weeks of age (N=6). Treadmill exercise began 2 weeks post-surgery and was performed for 30 minutes, 5 days a week, for 2 or 6 weeks at intense (16 m/min, 15° incline) or moderate (10 m/min, 5° incline) levels. Histomorphometric assessment of cartilage degradation (OARSI scoring), serum cytokine analysis, immunohistochemistry, and nanoCT analysis were conducted. Result. OARSI scoring confirmed OA induction 4 weeks post-DMM surgery, with forced exercise exacerbating cartilage degradation regardless of intensity. No significant genotype-dependent differences were observed. Serum analysis revealed elevated cytokine levels associated with OA and inflammation in KO mice compared to WT mice 4 and 8 weeks post-surgery (VEGF-A, MCP-1, CXCL10, RANTES, MIP1-alpha, MIP1-beta, and RANKL). The observed effects were often exacerbated by intense exercise but rarely by DMM surgery. NanoCT analysis demonstrated increased sclerotic bone changes after 6 weeks of forced exercise in KO mice compared to WT mice. Conclusion. Our results suggest an OA promoting effect of exercise in early disease stages of posttraumatic OA. Intense exercise induced inflammatory processes correlated to increased cytokine levels in the serum that might exacerbate OA pathogenesis in later stages. The neuropeptide alpha-CGRP might play a role in protecting against these adverse effects

Introduction. Knee Osteoarthritis (KOA) is a prevalent joint disease requiring accurate diagnosis and prompt management. The condition occurs due to cartilage deterioration and bone remodeling. Ultrasonography has emerged as a promising modality for diagnosing KOA. Medial meniscus extrusion (MME), characterized by displacement of medial meniscus beyond the joint line has been recognized as a significant marker of KOA progression. This study aimed to explore potentials Ultrasound findings in timely detection of MME and compare it to magnetic resonance imaging (MRI) as a reference standard. Method. A comprehensive literature search was performed in 4 databases from inception to May 1 2024. Two independent reviewers, initiated screening protocols and selected the articles based on inclusion and exclusion criteria and then extracted the data. Meta-analysis was conducted using R 4.3.2 packages mada and metafor. Result. A total of 2500 articles from 4 databases was retrieved; however, following the application of inclusion and exclusion criteria 23 articles were finally extracted. These studies collectively encompassed a total of 777 patients with mean age of 53.2±7.4. The mean BMI calculated for patients was 28.31 ± 2.45. All patients underwent non-weight bearing knee ultrasonography in supine position with 0° flexion. The reported medial meniscus extrusion was 2.58 mm for articles using MRI and 2.65 mm for those using Ultrasound (MD: 0.05 ± 0.12, P= 0.65, I. 2. : 54%). Our meta-analysis revealed insignificant difference between US and MRI. (SMD: 0.03, 95% CI: -0.18 _0.23, P= 0.77, I. 2. : 56%) Meta analysis for diagnostic accuracy measures yielded a pooled sensitivity and specificity of 90.8% and 77% (95% CI: 84.2% – 94.8%, 35.5% – 95.3%, respectively, I. 2. : 44%). Conclusion. Our results indicate a close alignment in the accuracy of measurements obtained using Ultrasound modality. The narrow range suggests a minimal discrepancy in MME values between MRI and ultrasound, highlighting their comparable precision in diagnostic assessments

Senescent chondrocyte and subchondral osteoclast overburden aggravate inflammatory cytokine and pro-catabolic proteinase overproduction, accelerating extracellular matrix degradation and pain during osteoarthritis (OA). Fibronectin type III domain containing 5 (FNDC5) is found to promote tissue homeostasis and alleviate inflammation. This study aimed to characterize what role Fndc5 may play in chondrocyte aging and OA development. Serum and macroscopically healthy and osteoarthritic cartilage were biopsied from patients with knee OA who received total knee replacement. Murine chondrocytes were transfected with Fndc5 RNAi or cDNA. Mice overexpressing Fndc5 (Fndc5Tg) were operated to have destabilized medial meniscus mediated (DMM) joint injury as an experimental OA model. Cellular senescence was characterized using RT-PCR analysis of p16INK4A, p21CIP1, and p53 expression together with ß-galactosidase activity staining. Articular cartilage damage and synovitis were graded using OARSI scores. Osteophyte formation and mechanical allodynia were quantified using microCT imaging and von Frey filament, respectively. Osteoclast formation was examined using tartrate-resistant acid phosphatase staining. Senescent chondrocyte and subchondral osteoclast overburden together with decreased serum FNDC5 levels were present in human osteoarthritic cartilage. Fndc5 knockdown upregulated senescence program together with increased IL-6, MMP9 and Adamts5 expression, whereas Alcian blue-stained glycosaminoglycan production were inhibited. Forced Fndc5 expression repressed senescence, apoptosis and IL-6 expression, reversing proliferation and extracellular matrix production in inflamed chondrocytes. Fndc5Tg mice showed few OA signs, including articular cartilage erosion, synovitis, osteophyte formation, subchondral plate sclerosis and mechanical allodynia together with decreased IL-6 production and few senescent chondrocytes and subchondral osteoclast formation during DMM-induced joint injury. Mechanistically, Fndc5 reversed histone H3K27me3-mediated IL-6 transcription repression to reduce reactive oxygen species production. Fndc5 loss correlated with OA development. It was indispensable in chondrocyte growth and anabolism. This study sheds light onto the anti-ageing and anti-inflammatory actions of Fndc5 to chondrocytes; and highlights the chondroprotective function of Fndc5 to compromise OA