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Arthritis Research & Therapy May 2024Due to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Accumulating evidence points to chondrocyte...
BACKGROUND
Due to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Accumulating evidence points to chondrocyte senescence as a key driver in OA development. This study aims to identify OA-specific microRNAs (miRNAs) targeting chondrocyte senescence to alleviate OA progression.
METHODS
We screened and identified miRNAs differentially expressed in OA and normal cartilage, then confirmed the impact of miR-653-5p on chondrocyte functions and senescence phenotypes through in vitro experiments with overexpression/silencing. We identified interleukin 6 (IL-6) as the target gene of miR-653-5p and confirmed the regulatory influence of miR-653-5p on the IL-6/JAK/STAT3 signaling pathway through gain/loss-of-function studies. Finally, we assessed the therapeutic efficacy of miR-653-5p on OA using a mouse model with destabilization of the medial meniscus.
RESULTS
MiR-653-5p was significantly downregulated in cartilage tissues and chondrocytes from OA patients. Overexpression of miR-653-5p promoted chondrocyte matrix synthesis and proliferation while inhibiting chondrocyte senescence. Furthermore, bioinformatics target prediction and the luciferase reporter assays identified IL-6 as a target of miR-653-5p. Western blot assays demonstrated that miR-653-5p overexpression inhibited the protein expression of IL-6, the phosphorylation of JAK1 and STAT3, and the expression of chondrocyte senescence phenotypes by regulating the IL-6/JAK/STAT3 signaling pathway. More importantly, the cartilage destruction was significantly alleviated and chondrocyte senescence phenotypes were remarkably decreased in the OA mouse model treated by agomiR-653-5p compared to the control mice.
CONCLUSIONS
MiR-653-5p showed a significant decrease in cartilage tissues of individuals with OA, leading to an upregulation of chondrocyte senescence phenotypes in the articular cartilage. AgomiR-653-5p emerges as a potential treatment approach for OA. These findings provide further insight into the role of miR-653-5p in chondrocyte senescence and the pathogenesis of OA.
Topics: MicroRNAs; Chondrocytes; Animals; Humans; Cellular Senescence; Osteoarthritis; Mice; Male; Interleukin-6; Mice, Inbred C57BL; STAT3 Transcription Factor; Cells, Cultured; Middle Aged; Female; Signal Transduction; Cartilage, Articular
PubMed: 38812033
DOI: 10.1186/s13075-024-03334-5 -
Scientific Reports May 2024Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between... (Observational Study)
Observational Study
Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between meniscus pathologies and KOA radiographic progression remains unclear. We conducted an observational study in the Osteoarthritis Initiative (OAI) cohort, with a 48-month follow-up. Meniscus pathology and synovitis were measured by MRI osteoarthritis knee score (MOAKS) at baseline and 24 months, and a comprehensive synovitis score was calculated using effusion and Hoffa synovitis scores. The knee osteoarthritis radiographic progression was considered that Kellgren-Lawrence (KL) grade and joint space narrowing (JSN) grade at 48 months were increased compared to those at baseline. This study included a total of 589 participants, with KL grades mainly being KL1 (26.5%), KL2 (34.1%), and KL3 (30.2%) at baseline, while JSN grades were mostly 0 at baseline. A logistic regression model was used to analyze the relationship between meniscus pathology, synovitis, and KOA progression. Mediation analysis was used to evaluate the mediation effect of synovitis. The average age of the participants was 61 years old, 62% of which were female. The medial meniscus extrusion was longitudinally correlated with the progression of KL (odds ratio [OR]: 2.271, 95% confidence interval [CI]: 1.412-3.694) and medial JSN (OR: 3.211, 95% CI: 2.040-5.054). Additionally, the longitudinal correlation between medial meniscus damage and progression of KOA (OR: 1.853, 95% CI: 1.177-2.941) and medial JSN (OR: 1.655, 95% CI: 1.053-2.602) was significant. Synovitis was found to mediate the relationship between medial meniscus extrusion and KL and medial JSN progression at baseline (β: 0.029, 95% CI: 0.010-0.053; β: 0.022, 95% CI: 0.005-0.046) and beyond 24 months (β: 0.039, 95% CI: 0.016-0.068; β: 0.047, 95% CI: 0.020-0.078). However, we did not find evidence of synovitis mediating the relationship between meniscal damage and KOA progression. Synovitis mediates the relationship between medial meniscus extrusion (rather than meniscus damage) and KOA progression.
Topics: Humans; Synovitis; Osteoarthritis, Knee; Female; Male; Middle Aged; Disease Progression; Aged; Magnetic Resonance Imaging; Menisci, Tibial; Meniscus; Radiography; Knee Joint
PubMed: 38811752
DOI: 10.1038/s41598-024-63291-6 -
Journal of Experimental Orthopaedics Jul 2024This study aimed to determine the respective roles of the anterior cruciate ligament (ACL) and the different components of the medial plane in the control of anterior...
All the menisco-ligamentary structures of the medial plane play a significant role in controlling anterior tibial translation and tibial rotation of the knee. Cadaveric study of 29 knees with the Dyneelax® laximeter.
PURPOSE
This study aimed to determine the respective roles of the anterior cruciate ligament (ACL) and the different components of the medial plane in the control of anterior tibial translation and internal and external tibial rotation.
METHODS
Twenty-nine fresh lower limbs, disarticulated at the hip, were tested in the anatomy laboratory. The following structures were isolated: the ACL, the anteromedial retinaculum (AMR), the medial collateral ligament (superficial and deep MCL), the posterior medial capsule (PMC) and the posterior horn of the medial meniscus (PHMM). The lower limb was positioned at 30° of flexion on the Dyneelax® laximeter (0.1 mm and 0.1° accuracies) and underwent anterior loads up to 200 N and internal and external tibial rotations sectioned from front to back. and the knee was then retested. The results were presented as relative gains in translation and rotations for each structure. Student's test and Wilcoxon tests were used.
RESULTS
The relative gains in translation for the ACL, AMR, superficial MCL, deep MCL, PMC and PHMM, respectively, were 42.9%, 6.7%, 7.4%, 6%, 7.5% and 11.6%. The relative gains in internal rotation for ACL, AMR, superficial MCL, deep MCL, PMC and PHMM, respectively, were 13%, 6.9%, 4.6%, 3.9%, 13% and 8%. The relative gains in external rotation for ACL, AMR, superficial MCL, deep MCL, PMC and medial meniscus, respectively, were 8.9%, 6%, 9.7%, 13.8%,11.2% and 8.5%. All the relative gains in translation, internal and external rotations were significant at each step of transection ( < 0.01).
CONCLUSIONS
The ligamentous structures of the medial plane constitute a functional unit in which each component has a specific passive contribution. This study highlights the importance of recognising the extent of the medial ligament tears and performing a medial side anatomic and individual reconstruction and a suture of a ramp lesion, in addition to an ACL surgery.
PubMed: 38807638
DOI: 10.1002/jeo2.12038 -
Life (Basel, Switzerland) May 2024The semimembranosus muscle inserts into several tendons that are associated with some pathologies. Although ultrasound is useful for studying, diagnosing, and managing...
The semimembranosus muscle inserts into several tendons that are associated with some pathologies. Although ultrasound is useful for studying, diagnosing, and managing these pathologies, the correct interpretation of any images requires a clear knowledge of the related anatomical structures and the inter-related functions. We studied 38 cryopreserved non-paired knees from adult anatomical specimens and 4 non-paired knees from 29 to 38-week-old fetuses. The semimembranosus muscle and its tendons were located, observed, and injected under ultrasound guidance. The macroscopic anatomy was studied using dissection and anatomical cuts and the tendons were analyzed histologically. Measurements of muscle were taken 10 cm from the medial epicondyle and just before the tendon divided. The ultrasound facilitated the identification of the different divisions of the tendon of semimembranosus muscle and the rotation of the muscle and tendon from medial to posterior. An anatomical study confirmed this rotation and revealed an average width, thickness, and diameter of 38.29 mm, 14.36 mm, and 112.64 mm, respectively. Important relationships were observed between the divisions of the main tendons and the medial collateral ligament, the posterior side of the knee and popliteus muscle. This information can help to explain knee pathologies and facilitate rehabilitation after surgery.
PubMed: 38792649
DOI: 10.3390/life14050631 -
Bioengineering (Basel, Switzerland) May 2024(1) Background: Bone bruises in acute anterior cruciate ligament (ACL) injuries are closely linked to the occurrence of simultaneous meniscal and cartilage damage.... (Review)
Review
(1) Background: Bone bruises in acute anterior cruciate ligament (ACL) injuries are closely linked to the occurrence of simultaneous meniscal and cartilage damage. Despite the frequent occurrence of associated injuries including bone bruises, meniscus, and cartilage damage in patients with ACL injuries, a systematic review of the relationships between the presence of bone bruises and the extent of meniscus and cartilage injuries has yet to be conducted. (2) Methods: Multiple comprehensive databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched for studies that evaluated the relationship between bone bruises and meniscus or cartilage injuries following ACL injuries. Study selection, data extraction, and meta-analysis were performed. The Methodological Index for Non-Randomized Studies (MINORS) was used for quality assessments, and Review Manager 5.3 was used for data analysis. (3) Results: Data were extracted from 22 studies encompassing a total of 2891 patients with ACL injuries. Among the included studies, six studies investigated the relationships between bone bruises and medial meniscus (MM) or lateral meniscus (LM) injuries, while three studies investigated the relationships between bone bruises and cartilage injuries. There were no significant correlations between the presence of bone bruises and MM injuries (relative risk (RR) = 1.32; = 0.61). A quantitative analysis indicated that individuals with bone bruises had a 2.71-fold higher likelihood of sustaining LM injuries than those without bone bruises (RR = 2.71; = 0.0003). The analysis confirmed a significant relationship between bone bruises and cartilage injuries (RR = 6.18; = 0.003). (4) Conclusions: Bone bruises occur most frequently in the lateral compartment. Bone bruises resulting from ACL injuries are related to accompanying LM injuries and cartilage injuries. Knowing these associations and the frequency of injuries may allow orthopedic surgeons to promptly address ACL-related meniscus and cartilage injuries on MRI results and in future clinical practice.
PubMed: 38790382
DOI: 10.3390/bioengineering11050515 -
Journal of Orthopaedic Case Reports May 2024The relationship between physical trauma and subsequent symptoms of rheumatoid arthritis (RA) has been described in the past though onset of newer disease of RA in...
INTRODUCTION
The relationship between physical trauma and subsequent symptoms of rheumatoid arthritis (RA) has been described in the past though onset of newer disease of RA in apparently normal patient is doubtful. Trauma can cause precipitation of RA symptoms. Such trauma includes fractures, joint injuries, road traffic accidents, and also surgeries and deliveries. Although post-traumatic osteoarthritis following anterior cruciate ligament (ACL) injury is more common pathology, association of RA following ACL injury has not been reported in the literature. This case report highlights on one rare incidental diagnosis of RA postoperatively in a patient with traumatic ACL tear with previously no features of RA and how patient was managed successfully both by surgical and by medical management.
CASE REPORT
A 30-year-old male patient presented to us with complaints of pain over right knee associated with recurrent swelling, instability, clicking sounds, and occasional locking episodes since 6 months following twisting injury with no other symptoms in other joints of the body. Based on clinicoradiological workup, the diagnosis of traumatic complete ACL tear with medial meniscus bucket handle tear of body and posterior horn with early osteoarthritic changes was made. The patient was operated with ACL reconstruction with quadrupled hamstring graft, partial medial meniscectomy and debridement + microfracture for cartilage defects. The patient was worked up for inflammatory arthritis post operatively considering unusual synovitis of knee. Based on histopathological and serological investigations (rheumatoid factor and anticitrullinated protein antibody), the patient was put on disease modifying antirheumatoid drugs for 1 year. At 1-year follow-up, the patient was back to his normal activities with full range of movements with Lysholm Knee Score of 89.
CONCLUSION
Traumatic ACL tear can result in onset of RA following trauma and needs to be worked up further when there are findings of unusual synovitis or cartilage damage arthroscopically. Such association is rare and concomitant diagnosis of RA or other inflammatory arthritis can be easily missed out if not addressed properly.
PubMed: 38784878
DOI: 10.13107/jocr.2024.v14.i05.4444 -
JFMS Open Reports 2024An 11-year-old female neutered domestic shorthair cat was referred for surgical management of a traumatic right stifle luxation. Orthopaedic examination of the affected...
CASE SUMMARY
An 11-year-old female neutered domestic shorthair cat was referred for surgical management of a traumatic right stifle luxation. Orthopaedic examination of the affected stifle under general anaesthesia revealed joint effusion and craniocaudal and rotational instability. Cranial displacement of the tibia with respect to the femur and infrapatellar pad sign were identified on radiography. Intraoperatively, complete rupture of both cruciate ligaments and marked disruption of the mid and caudal poles of the medial and lateral menisci were observed. Both collateral ligaments appeared intact. The remnants of the injured cruciate ligaments were removed, and medial and lateral caudal hemimeniscectomies were performed. A tibial plateau levelling osteotomy (TPLO) was performed to address the craniocaudal stifle instability. Intraoperative assessment of the stifle revealed persistent instability with cranial tibial translation, internal and external rotation, and a positive caudal draw test. A lateral augmentation suture was employed to address the persistent cranial tibial translation and internal rotation. To successfully neutralise caudocranial and external rotational instability secondary to the caudal cruciate ligament deficiency, a medial augmentation suture was placed with the aid of three interference screws. Stifle stability was achieved. A modified Robert-Jones bandage was kept on for 24 h postoperatively. An excellent outcome was achieved, with successful limb function restoration.
RELEVANCE AND NOVEL INFORMATION
This case report represents the first documented instance of feline traumatic stifle luxation repair by combining a corrective tibial osteotomy and extra-articular augmentation. Notably, it introduces the novel technique of implementing a TPLO with medial and lateral augmentation sutures to address multidirectional stifle instability.
PubMed: 38784085
DOI: 10.1177/20551169241247439 -
Journal of Orthopaedic Science :... May 2024To the best of our knowledge, no prior studies have identified any risk factors for subchondral insufficiency fractures of the medial tibial condyle. This study aimed to...
BACKGROUND
To the best of our knowledge, no prior studies have identified any risk factors for subchondral insufficiency fractures of the medial tibial condyle. This study aimed to explain relationships between subchondral insufficiency fractures of the medial tibial condyle and the meniscus status, lower extremity alignment, or osteoporosis.
METHODS
This retrospective study included 325 consecutive patients whose chief complaint is knee joint pain and who had visited one institution between April 2016 and March 2021, of which 70 patients (8 men and 62 women) who had suspected subchondral insufficiency fractures of the medial tibial condyle had undergone magnetic resonance imaging and radiographic examination. These patients were divided into two groups based on the results of their magnetic resonance imaging: the insufficiency fracture group included 46 patients who had subchondral insufficiency fractures of the medial tibial condyle and the nonfracture group included 24 patients without fractures. The meniscus injury and medial meniscus extrusion (MME) were evaluated by using magnetic resonance imaging. The Kellgren-Lawrence grade, the femorotibial angle, and the percent mechanical axis (%MA) were evaluated with the use of knee radiographs. T-scores were also measured by using dual-energy X-ray absorptiometry with a bone densitometer.
RESULTS
MME were significantly larger and the %MA was significantly smaller in the insufficiency fracture group than that in the nonfracture group. The prevalence of medial meniscus injuries and pathological MME were higher in the insufficiency fracture group than those in the nonfracture group. The prevalence of varus knee and osteoporosis did not vary remarkably different between the two groups.
CONCLUSION
The patients who had insufficiency fractures of the medial tibial condyle tended to have medial meniscus extrusion.
PubMed: 38777662
DOI: 10.1016/j.jos.2024.04.010 -
The American Journal of Sports Medicine Jun 2024Satisfactory clinical results of meniscal allograft transplantation (MAT) have been reported in recent years. However, it remains unclear whether the clinical outcomes...
BACKGROUND
Satisfactory clinical results of meniscal allograft transplantation (MAT) have been reported in recent years. However, it remains unclear whether the clinical outcomes of MAT when combined with an osteotomy are inferior to those of isolated MAT.
PURPOSE
To compare the survival rates and clinical outcomes of patients who received isolated medial MAT with those of patients undergoing medial MAT combined with high tibial osteotomy (HTO).
STUDY DESIGN
Cohort study; Level of evidence, 3.
METHODS
A total of 55 patients underwent arthroscopic medial MAT using the soft tissue technique and HTO (mean age, 41.3 ± 10.4 years; 9 female); after fuzzy case-control matching on demographics, 55 controls who underwent isolated medial MAT were also included. Survival analyses were performed using the Kaplan-Meier method with surgical failure, clinical failure (Lysholm score, <65), and reoperation as endpoints. Subjective clinical scores were collected preoperatively and at the final follow-up.
RESULTS
The mean follow-up time was 5.4 years, up to 8 years. All outcomes significantly improved at the last follow-up ( < .001). No differences were identified between MAT and MAT + HTO groups preoperatively and at the last follow-up ( > .05). At the final follow-up, 8 of 55 (14.5%) of the MAT + HTO patients and 9 of 55 (16.4%) of the MAT patients had a Lysholm score <65 ( = .885). Overall, 90% of the patients declared they would repeat the surgery regardless of the combined procedure. Surgical failure was identified in 6 of 110 (5.5%) patients: 5 of 55 (9.1%) in the MAT + HTO group and 1 of 55 (1.8%) in the MAT group ( = .093). Clinical failure was identified in 19 of 110 (17.3%) patients: 11 of 55 (20%) in the MAT + HTO group and 8 of 55 (14.5%) in the MAT group ( = .447). A significantly lower survivorship from surgical failure was identified in the MAT + HTO group (hazard ratio, 5.1; = .049), while no differences in survivorship from reoperation and clinical failure were identified ( > .05).
CONCLUSION
Patients undergoing medial MAT + HTO showed similar clinical results to patients undergoing isolated medial MAT at midterm follow-up, and thus a surgically addressed malalignment does not represent a contraindication for medial MAT. However, the need for a concomitant HTO is associated with a slightly higher failure rate over time.
Topics: Humans; Female; Male; Adult; Osteotomy; Case-Control Studies; Middle Aged; Menisci, Tibial; Follow-Up Studies; Tibia; Treatment Outcome; Reoperation; Allografts; Transplantation, Homologous; Arthroscopy
PubMed: 38767945
DOI: 10.1177/03635465241248822 -
Drug Design, Development and Therapy 2024Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata-...
Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Mechanisms of Radix Rehmanniae Praeparata - Angelica Sinensis - Radix Achyranthis Bidentatae in Treating Knee Osteoarthritis.
BACKGROUND
Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata- Angelica Sinensis-Radix Achyranthis Bidentatae (RAR) has often been used in effective prescriptions for KOA as the main functional drug, but its underlying mechanism remains unclear. Therefore, network pharmacology and verification experiments were employed to investigate the impact and mode of action of RAR in the treatment of KOA.
METHODS
The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK-8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments.
RESULTS
In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats.
CONCLUSION
RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.
Topics: Animals; Angelica sinensis; Osteoarthritis, Knee; Drugs, Chinese Herbal; Mice; Achyranthes; Network Pharmacology; Rehmannia; Molecular Docking Simulation; Cells, Cultured; Chondrocytes; Male; Mice, Inbred C57BL; Rats
PubMed: 38765877
DOI: 10.2147/DDDT.S455006