Correlation of meniscus tear type with synovial inflammation and the therapeutic potential of docosapentaenoic acid.

BACKGROUND: Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and the key inflammatory mediators of synovium induced by different types of meniscal tears remain unclear. METHODS: Magnetic resonance imaging (MRI) was employed to identify the type of meniscus tear, and the quantification of synovial inflammation was assessed through H&E staining assay. Transcription and expression levels of IL-1ß and IL-6 were evaluated using bioinformatics, ELISA, RT-qPCR, and IHC of CD68 staining assays. The therapeutic potential of Docosapentaenoic Acid (DPA) was determined through network pharmacology, ELISA, and RT-qPCR assays. The safety of DPA was assessed using colony formation and EdU staining assays. RESULTS: The results indicate that both IL-1ß and IL-6 play pivotal roles in synovitis pathogenesis, with distinct expression levels across various subtypes. Among tested meniscus tears, oblique tear and bucket handle tear induced the most severe inflammation, followed by radial tear and longitudinal tear, while horizontal tear resulted in the least inflammation. Furthermore, in synovial inflammation induced by specific meniscus tears, the anterior medial tissues exhibited significantly higher local inflammation than the anterior lateral and suprapatellar regions, highlighting the clinical relevance and practical guidance of anterior medial tissues' inflammatory levels. Additionally, we identified the essential omega-3 fatty acid DPA as a potential therapeutic agent for synovitis, demonstrating efficacy in blocking the transcription and expression of IL-1ß and IL-6 with minimal side effects. CONCLUSION: These findings provide valuable insights into the nuanced nature of synovial inflammation induced by various meniscal tear classifications and contribute to the development of new adjunctive therapeutic agents in the management of synovitis.

Risk Factors Affecting the Survival Rate of Collagen Meniscal Implant for Partial Meniscal Deficiency: An Analysis of 156 Consecutive Cases at a Mean 10 Years of Follow-up.

BACKGROUND: Collagen meniscal implant (CMI) is a biologic scaffold that can be used to replace meniscus host tissue after partial meniscectomy. The short-term results of this procedure have already been described; however, little is known about risk factors for failure. PURPOSE: To determine the factors that predict failure of meniscal scaffold implantation in a large series of patients treated at a single institution and to better define the indications for surgery. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The analysis included 186 consecutive patients with a minimum 5-year follow-up who underwent CMI scaffold implantation or combined procedures. Patients' characteristics and details of the surgery were obtained via chart review. Patients with a Lysholm score <65 were considered to have experienced clinical failure. Surgical failure was defined as partial or total scaffold removal. RESULTS: The final analysis included 156 patients (84%) at a mean follow-up of 10.9 ± 4.3 years. The patients' mean age at surgery was 42.0 ± 11.1 years, and the survival rate was 87.8%. Subgroup analysis identified Outerbridge grade 3-4 (Hazard ratio [HR], 3.8; P = .004) and a lateral meniscal implant (HR, 3.2; P = .048) as risk factors for failure. The survival rate was 90.4% for medial implants and 77.4% for lateral implants. An Outerbridge grade 3-4 (HR, 2.8; P < .001) and time from meniscectomy to scaffold >10 years (HR, 2.8; P = .020) were predictive of surgical or clinical failure. CONCLUSION: CMI for partial meniscal deficiency provided good long-term results, with 87.8% of the implants still in situ at a mean 10.9 years of follow-up. Outerbridge grade 3-4, lateral meniscal implants, and longer time from the meniscectomy to implantation of the CMI were identified as risk factors for clinical and surgical failure.

Anatomical description and short-term follow up clinical results for ultrasound-guided injection of medial collateral ligament bursa: New conservative treatment option for symptomatic degenerative medial meniscus tear.

BACKGROUND: In this study, we investigated newly developed ultrasound (US)-guided medial collateral ligament (MCL) bursa injection as a conservative therapy for symptomatic degenerative medial meniscal (MM) tears. We aimed to describe the anatomical target and precise technique of this injection, confirm its accuracy using fresh cadaveric knees, and then evaluate preliminary clinical outcomes. METHODS: Anatomical studies were performed on three fresh cadavers. For the clinical study, 50 patients with medial knee joint pain without knee osteoarthritis were treated with US-guided MCL bursa injection. Severity of pain was assessed pre-injection, and 1 week and 4 weeks post-injection using a 0-10 numerical rating scale (NRS). Clinical success was defined as a full return to daily activities. All patients underwent magnetic resonance imaging (MRI) within 1 week of the first injection. Patients who underwent surgery within 12 months of the first injection were investigated as clinically unsuccessful cases, and MRI and arthroscopic findings were examined. RESULTS: Compared with pre-injection (6.8 ±â€¯1.2), the average NRS score was significantly lower at 1 week (1.8 ±â€¯2.0) and at 4 weeks (1.5 ±â€¯1.7) post-injection (both P < 0.01). The primary clinical success rate was 76.0%, and injection-related adverse events were not observed. Nine patients underwent surgery (arthroscopic surgery for degenerative flap tear (n = 7) and high tibial osteotomy for medial meniscus posterior root tear and proximal tibial malalignment (n = 2)). CONCLUSIONS: US-guided MCL bursa injection is safe, reproducible, and effective for symptomatic MM degenerative tears. However, US-guided injections of the MCL bursa may be ineffective for flap tears and posterior root tears.

Conservative vs. surgical approach for degenerative meniscal injuries: a systematic review of clinical evidence.

OBJECTIVE: Analyzing the available evidence by comparing the role of arthroscopic surgery and conservative treatment in the management of degenerative meniscopathy. MATERIALS AND METHODS: A literature search was carried out on the PubMed, EMBASE, Scopus, and PEDro databases in May 2019 to identify all the randomized controlled trials (RCTs) comparing arthroscopic surgery to conservative management of painful but stable degenerated menisci. The quality of the RCTs was assessed using the Cochrane Risk of Bias Assessment. RESULTS: A total of 10 studies, including 1525 patients and dealing with conservative treatment vs. arthroscopic surgery were included in this review. In eight studies the effectiveness of exercise therapy was compared to surgery; in one study the effectiveness of intra-articular steroid injection was compared to surgery; in one study the effectiveness of placebo surgery was compared to partial meniscectomy. In all studies, no significant inter-group difference in terms of knee pain and knee function were observed at any follow-up evaluation. CONCLUSIONS: Degenerative meniscal tears, without symptoms of locking and catching, can be successfully managed by a proper regimen of physical therapy as a first line treatment. Surgical approach might be considered in case of poor response after conservative treatment.

Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model.

OBJECTIVE: To investigate whether the effects of nerve growth factor (NGF) inhibition with tanezumab on rats with medial meniscal tear (MMT) effectively model rapidly progressive osteoarthritis (RPOA) observed in clinical trials. METHODS: Male Lewis rats underwent MMT surgery and were treated weekly with tanezumab (0.1, 1 or 10 mg/kg), isotype control or vehicle for 7, 14 or 28 days. Gait deficiency was measured to assess weight-bearing on the operated limb. Joint damage was assessed via histopathology. A second arm, delayed onset of treatment (starting 3-8 weeks after MMT surgery) was used to control for analgesia early in the disease process. A third arm, mid-tibial amputation, evaluated the dependency of the model on weight-bearing. RESULTS: Gait deficiency in untreated rats was present 3-7 days after MMT surgery, with a return to normal weight-bearing by days 14-28. Prophylactic treatment with tanezumab prevented gait deficiency and resulted in more severe cartilage damage. When onset of treatment with tanezumab was delayed to 3-8 weeks after MMT surgery, there was no increase in cartilage damage. Mid-tibial amputation completely prevented cartilage damage in untreated MMT rats. CONCLUSIONS: These data suggest that analgesia due to NGF inhibition during the acute injury phase is responsible for increased voluntary weight-bearing and subsequent cartilage damage in the rat MMT model. This model failed to replicate the hypotrophic bone response observed in tanezumab-treated patients with RPOA.

Local Administration of Simvastatin Stimulates Healing of an Avascular Meniscus in a Rabbit Model of a Meniscal Defect.

BACKGROUND: Repair of an avascular meniscus is challenging because of its low capacity for healing. Several reports have shown that simvastatin stimulates the anabolic activity of intervertebral fibrochondrocytes, suggesting that simvastatin may be used for the treatment of meniscal defects. PURPOSE: To test whether the local administration of simvastatin stimulates healing of an avascular meniscus in rabbits. STUDY DESIGN: Controlled laboratory study. METHODS: In 30 Japanese White rabbits, a cylindrical defect (1.5-mm diameter) was introduced into the avascular zone of the anterior part of the medial meniscus in bilateral knees. Either a gelatin hydrogel (control group) or simvastatin-conjugated gelatin hydrogel (simvastatin group) was implanted into the defect. Histological assessments were performed using qualitative scoring systems, and immunohistochemical analysis was performed at 12 weeks after surgery. The occupation ratio (OR) and safranin O staining occupation ratio (SOR) were evaluated quantitatively at each time point. Stiffness of the regenerated tissue was analyzed biomechanically at 12 weeks after surgery. Rabbit meniscal cells were cultured in the presence or absence of 0.5 µM simvastatin, and then real-time polymerase chain reaction was performed to evaluate gene expression. RESULTS: The qualitative score was significantly higher in the simvastatin group after 8 and 12 weeks (P = .031 and .035, respectively). The mean OR and SOR were also significantly higher in the simvastatin group (OR at 8 weeks: 0.396 ± 0.019 [control] vs 0.564 ± 0.123 [simvastatin], P = .008; OR at 12 weeks: 0.451 ± 0.864 [control] vs 0.864 ± 0.035 [simvastatin], P = .001; SOR at 8 weeks: 0.071 ± 0.211 [control] vs 0.487 ± 0.430 [simvastatin], P = .009; SOR at 12 weeks: 0.093 ± 0.088 [control] vs 0.821 ± 0.051 [simvastatin], P = .006). Immunohistochemical analysis showed that at 12 weeks, the reparative tissue was more strongly positive for type I collagen (COL1), type II collagen (COL2), bone morphogenetic protein 2 (BMP-2), and BMP-7 in the simvastatin group than in the control group. Biomechanical analysis showed significantly higher stiffness in the simvastatin group (2.417 ± 1.593 N/ms [control] vs 5.172 ± 1.078 N/ms [simvastatin]; P = .005). In rabbit meniscal cells, BMP-2 and BMP-7 were upregulated after 4 and 8 hours and after 7 and 14 days, whereas COL1A1 and COL2A1 were significantly upregulated by simvastatin after 7 and 14 days. CONCLUSION: The local administration of simvastatin promotes the regeneration of an avascular meniscus in the rabbit model of a meniscal defect. The mechanism may involve the upregulation of BMPs and the subsequent upregulation of COL1 and COL2. CLINICAL RELEVANCE: This study suggests that simvastatin stimulated intrinsic healing of an avascular meniscus. The local administration of simvastatin is safe and inexpensive and seems to be a promising treatment of meniscal injuries.

[Effect of HBP-A on meniscal injury and pathological hypertrophy and calcification of the meniscus].

OBJECTIVE: To investigate the effect of HBP-A on meniscal injuries and the expressions of genes associated with pathological hypertrophy and calcification of the meniscusinduced by abnormal loading. METHODS: Bovine meniscus explants were subjected to 25% strain at 0.3 Hz for 3 h and treated with 0.6 mg/mL of HBP-A. The cell viability in the meniscus explants after 72 hin culture was determined using live/dead staining and the expression levels of genes associated with pathological hypertrophy and calcification of the meniscus (ANKH, ENPP1, ALP, MMP13, and IL-1) were measured using real-time PCR and Western blotting. The conditioned medium was collected for testing sulfated glycosaminoglycan (GAG) release. RESULTS: The number of dead cells, loss of proteoglycan content, and the expressions of ANKH, ENPP1, ALP and MMP13, and IL-1 at both the mRNA and protein levels were all significantly lower in the meniscus explants treated with 0.6 mg/mL HBP-A than in the explants with only 25% abnormal pressure stimulation (n=3, P<0.05). CONCLUSION: HBP-A can effectively alleviate meniscal injuries induced by abnormal loading and suppress the expressions of genes related with pathological hypertrophy and calcification of the meniscus, and can serve as a potential drug for treatment of knee osteoarthritis.