Ryuichiro Akagi

Chiba University, Tiba, Chiba, Japan

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Publications (17)51.12 Total impact

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    ABSTRACT: This study investigated the effect of MMP-13 gene knock down on cartilage degradation by injecting small interfering RNA (siRNA) into knee joints in a mouse model of osteoarthritis (OA). OA was induced in male C57BL/6 mice by destabilization of medial meniscus (DMM) surgery. Change of Mmp13 expression over time was determined by qPCR analysis from 3 days to 6 weeks after surgery. Mmp13 and control chemically modified siRNA were injected into the knee joint 1 week after surgery and expression levels were assessed in synovium by qPCR 48 h later. Cartilage degradation was histologically assessed 8 weeks after DMM surgery according to OARSI recommendations. Mmp13 expression levels were elevated 1 week after surgery and peaked at 77 fold at 2 weeks compared to expression at 3 days. A 55% decrease of Mmp13 levels in cartilage was observed 48 h after injection of Mmp13 siRNA (p = 0.05). Significant reduction in the histological score at 8 weeks after surgery was observed in the Mmp13 siRNA-treated group compared to the control siRNA group (p < 0.001). Intra-articular injection of Mmp13 siRNA at the early phase of OA development resulted in effective knock down of Mmp13 expression and delay in cartilage degradation in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
    Journal of Orthopaedic Research 05/2014; · 2.88 Impact Factor
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    ABSTRACT: Osteoarthritis leads to pain and loss of function in affected joints. Gait disturbance results from these symptoms of OA, and gait analysis can be important to evaluate the progression of OA. The purpose of this study was to analyze gait pattern in a rodent model of OA and to assess the effects of intra-articular injection of hyaluronan (IAI-HA) by gait analysis, along with histological evaluation. OA was induced by destabilization of the medial meniscus (DMM) of C57BL/6 mice. IAI-HA started 3 weeks after DMM surgery. Mice were allocated to three groups and were given either 800-kDa HA (800-HA), 6000-kDa HA (6000-HA) or saline. We compared these three groups with a sham group by gait analysis using CatWalk (TM). Histological evaluation was performed to assess articular cartilage changes in the knee joints. Mice injected with 800-HA or 6000-HA showed gait patterns similar to that of the sham mice, while the saline-injected group showed gait disturbances 12 and 16 weeks after DMM surgery. Histological changes in articular cartilage were similar among the 800-HA, 6000-HA and saline-treated groups, demonstrating OA progression throughout the experimental time points. Positive gait-related effects of IAI-HA might occur by its pain relieving effect and/or by preventing contracture. IAI-HA prevented gait disturbances in the DMM model, but did not prevent histological changes associated with OA progression.
    Osteoarthritis and Cartilage 04/2014; · 4.26 Impact Factor
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    ABSTRACT: To estimate the long-term possibility of needing surgery on contralateral knees that were asymptomatic at the time of initial discoid lateral menisci (DLM) surgeries, a minimum of 10 years of follow-up was performed after unilateral surgery for a torn DLM. Eligible patients had received arthroscopic meniscectomy between 1986 and 2001 for unilateral torn DLM. Patients with symptomatic contralateral knees at the time of initial surgery were excluded. Among these patients, only those aged no more than 20 years at the time of surgery were included in the study. Ultimately, 30 contralateral knees were followed for an average of 16.6 years after the initial knee surgery. Types of menisci were examined from operative records employing Watanabe's classification. When surgical treatment was necessary on contralateral knee, time interval from initial surgery to the second surgery was recorded. Patients were divided into two groups: those who needed surgical treatment on their contralateral knees (surgery group: S group) and those who did not need surgical treatment on their contralateral knees (non-surgery group: N group). Age at the time of initial surgery, sex, and type of menisci were examined and compared between the two groups. Seven of the 30 knees received arthroscopic surgery during the follow-up period (at an average of 1.6 years after the initial surgery). The rest of the 77% of contralateral knees survived a follow-up period of at least 10 years without requiring surgery. A higher percentage of female patients needed contralateral knee surgeries (30%, 6/20 patients) compared with male patients (10%, 1/10 patients). The possibility for needing surgery on the contralateral knee was highest in the first 2 years and decreased drastically thereafter.
    Asia-Pacific Journal of Sports Medicine, Arthroscopy, Rehabilitation and Technology. 01/2014; 1(1):38–41.
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    ABSTRACT: Objective Osteoarthritis leads to pain and loss of function in affected joints. Gait disturbance results from these symptoms of OA, and gait analysis can be important to evaluate the progression of OA. The purpose of this study was to analyze gait pattern in a rodent model of OA and to assess the effects of intra-articular injection of hyaluronan (IAI-HA) by gait analysis, along with histological evaluation. Design OA was induced by destabilization of the medial meniscus (DMM) of C57BL/6 mice. IAI-HA started 3 weeks after DMM surgery. Mice were allocated to three groups and were given either 800-kDa HA (800-HA), 6000-kDa HA (6000-HA) or saline. We compared these three groups with a sham group by gait analysis using CatWalk TM. Histological evaluation was performed to assess articular cartilage changes in the knee joints. Results Mice injected with 800-HA or 6000-HA showed gait patterns similar to that of the sham mice, while the saline-injected group showed gait disturbances 12 and 16 weeks after DMM surgery. Histological changes in articular cartilage were similar among the 800-HA, 6000-HA and saline-treated groups, demonstrating OA progression throughout the experimental time points. Positive gait-related effects of IAI-HA might occur by its pain relieving effect and/or by preventing contracture. Conclusion IAI-HA prevented gait disturbances in the DMM model, but did not prevent histological changes associated with OA progression.
    Osteoarthritis and Cartilage 01/2014; · 4.26 Impact Factor
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    ABSTRACT: BACKGROUND:: Cystic mass lesions in the popliteal area, called popliteal cysts or Baker's cysts, are usually minimally symptomatic and not related to intra-articular morbidity in the pediatric population. Although multiple studies have described cases of spontaneous resolution over a period of several months to a few years, others still consider surgical treatment necessary. Furthermore, no previous studies have used magnetic resonance imaging (MRI) to confirm the disappearance of popliteal cysts. In this retrospective study, we reviewed records of patients with popliteal cysts to investigate the natural history of this disease. METHODS:: The medical records of patients with popliteal cysts followed for at least 12 months were retrospectively reviewed. The patient set comprised of 17 knees in 15 males and 3 knees in 2 females. Mean age was 5.6±2.0 years (range, 1.8 to 11.4 y) at their initial visit to the clinic, and mean follow-up period was 53.1±31.6 months (range, 12.6 to 147.8 mo). MRI findings were reviewed for the 16 knees in 13 patients who had undergone MRI. Symptoms and clinical course were extracted from the medical records of all the study subjects and analyzed. RESULTS:: Although 6 knees (30%) had histories of pain in the popliteal area, no patient complained of pain at their initial visit. Seventeen cysts (85%) naturally decreased in size or disappeared on clinical examination and/or ultrasound. Cysts confined to either the gastrocnemio-semimembranosus bursa or the subgastrocnemius bursa according to the MRI findings were classified as type I, and cysts which occupied both bursae were classified as type II. Eight knees received MRI examination more than once, and complete disappearance was confirmed in 5 of these knees. All type II cysts converted to type I, and all cysts which completely disappeared were type I before disappearance. CONCLUSIONS:: The MRI findings in our study population confirmed that popliteal cysts in pediatric populations can be expected to completely resolve in due course without treatment. LEVEL OF EVIDENCE:: Therapeutic study Level IV (Case series).
    Journal of pediatric orthopedics 04/2013; 33(3):262-268. · 1.23 Impact Factor
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    ABSTRACT: To investigate the longitudinal angiogenic activity of subchondral bone and cartilage during the progression of osteoarthritis (OA) using a rabbit model of OA. OA was surgically induced by anterior cruciate ligament transaction (ACLT) in left knee of 12 months old female New Zealand white rabbits (n = 33). Histological examination, immunohistochemistry, and angiogenic activity assay was done at 0, 2, 4, 6, 8, 12 weeks after ACLT. Histologic evaluation was performed with haematoxylin and eosin, safranin-O staining to assess the OA change of medial femoral condyle (MFC) and lateral femoral condyle (LFC). CD31 immunohistochemistry was performed to confirm the vascular invasion at osteochondral junction. A co-cultured tubule formation assay was conducted to evaluate angiogenic activity of the subchondral bone and cartilage of MFC and LFC as well as synovium. Association between histological changes, angiogenic activity, and vascular invasion were evaluated. OA changes increased in a time-dependent manner both in MFC and LFC. Angiogenic activity of subchondral bone showed a monomodal change during the OA progression, achieved a peak in the early to progressive stage and decreased to normal level in the late stage of OA. Surge of vascular invasion was observed following the increase of angiogenic activity in the progressive stage of OA. Angiogenic activity of cartilage did not change during the course of OA progression. Angiogenic activity of subchondral bone was elevated in the early to progressive stage of OA and vascular invasion into the osteochondral junction followed.
    Osteoarthritis and Cartilage 09/2012; 20(12):1574-82. · 4.26 Impact Factor
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    ABSTRACT: Anterior dislocation after total knee arthroplasty (TKA) is rare; 9 cases have been reported in the English literature. Five patients sustained subluxation, with recurvatum as the clinical manifestation, and 4 patients sustained complete dislocation, usually accompanying other serious complications.This article describes a case of complete dislocation that developed atraumatically 16 years after TKA and was characterized by dislocation in extension and spontaneous reduction in flexion. Revision TKA was planned, with several alternative procedures under consideration, ranging in degree of invasiveness from simple polyethylene exchange to conversion to a hinge-typed prosthesis. Intraoperatively, extensive areas of blackened synovium and posterior-dominant polyethylene wear existed medially and laterally. Considering the patient's age of 82 years, low activity level in activities of daily living, edematous skin, and number of stable components, we performed simple polyethylene exchange to a cruciate-retaining component that left the partial metal defect in the tibial plate untouched. Successful outcome was achieved for >2 years. The dislocation mechanism was polyethylene thinning, leading to relative valgus and anteroposterior instability that aggravated the anterior cruciate ligament dysfunction, which is speculated as the inherent key causative factor in every TKA.Complete dislocation, usually accompanying other complications, requires prompt treatment because the possibility of serious consequences exists. Due to the absence of a gold standard, the treatment of choice needs to be made on a case-by-case basis.
    Orthopedics 04/2012; 35(4):e585-8. · 1.05 Impact Factor
  • Osteoarthritis and Cartilage 01/2012; 20:S107-S108. · 4.26 Impact Factor
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    ABSTRACT: Partial-thickness articular cartilage defects (PTCDs) do not heal spontaneously and are thought to be a predisposing factor for the development of osteoarthritis. Younger and smaller animals have a better healing capacity for many types of injuries including those to articular cartilage. Our aim was to examine the longitudinal histological changes of immature murine articular cartilage after the creation of small PTCDs and to compare them to PTCDs in mature cartilage. Single linear PTCDs were created in 3-week-old and 16-week-old rats in the direction of joint motion. At 6 and 12 weeks after PTCD creation, histological changes were examined in the defect sites and surrounding cartilage. Immature cartilage showed a higher repair capability than mature cartilage. Although repaired immature cartilage had fibrocartilage, it exhibited better quality than any PTCD model, except for a fetus model and comparable quality to full-thickness cartilage defects (FTCD) after bone marrow stimulation. Elucidation of the underlining mechanisms that immature cartilage possesses for repairing PTCDs is necessary in order to aid the prevention or develop treatment for osteoarthritis.
    Cell and Tissue Research 11/2011; 346(2):263-71. · 3.68 Impact Factor
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    ABSTRACT: Several MRI-based evaluation systems for osteoarthritis (OA) of the knee have been developed. Among them the whole-organ magnetic resonance imaging score (WORMS), which evaluates the status of the entire knee joint, appears to be representative. We developed an irregularity index system to measure irregularities of the contours of the femoral condyle on MRI. Only the contour of the condyle was assessed by the irregularity index, whereas several items comprising the knee joint were taken into account by WORMS. This study compared the irregularity index and WORMS in terms of their correlations with clinical scores. Thirty-one medial-type OA knees were studied. Kellgren-Lawrence grading was used for X-ray grading: 8 were grade II, 11 were grade III, and 12 were grade IV. Japanese Orthopaedic Association scores and Japanese knee osteoarthritis measure scores were used for clinical assessments. We determined the correlations between MRI-based assessment scores and clinical scores. Both the irregularity index and WORMS exhibited positive correlations with these clinical scores. The irregularity index was associated with bone cysts of the medial compartment and menisci in the articular features of WORMS. These MRI-based methods are useful for evaluating OA severity. However, the irregularity index may have advantages over WORMS because of its semi-automatic features.
    Journal of Orthopaedic Science 05/2011; 16(4):369-75. · 0.96 Impact Factor
  • Osteoarthritis and Cartilage 01/2011; 19. · 4.26 Impact Factor
  • Osteoarthritis and Cartilage 01/2011; 19. · 4.26 Impact Factor
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    ABSTRACT: Synovial haemangioma of the knee joint is a relatively rare benign condition with around 200 reported cases. We have recently encountered two cases of synovial haemangioma of the knee joint which preoperative MRI had assessed as highly suspect and which arthroscopic resection and subsequent histological examinations confirmed as synovial hemangiomas. Published studies have identified the following as characteristic MRI features of synovial haemangioma: homogenous low intensity to iso-intensity on T1 sequence; and heterogeneous high intensity with low-intensity septa or spots within the lesion on T2 sequence. However, several other intra-knee disorders mimic these characteristics. In our two cases, we found that gadolinium (Gd)-enhanced images, which have been relatively rarely discussed in the literature, were useful for making the diagnosis and for determining the extent of this condition. These images also were very helpful during arthroscopic excision of the lesion. Nonetheless, even after Gd enhancement, differentiating between malignant conditions such as synovial sarcoma and haemangioma solely from MRI findings is still difficult.
    The Knee 10/2010; 18(6):509-11. · 2.01 Impact Factor
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    ABSTRACT: The optimal timing for surgical intervention in cases of lumbar disc herniation is debatable. This retrospective study sought to determine whether early surgical intervention resulted in greater improvement in clinical outcomes. A total of 46 patients with lumbar disc herniation treated by microendoscopic discectomy were reviewed. Surgery was performed when leg pain persisted despite adequate conservative treatment. The patients were divided into two groups according to the duration of symptoms before surgery, the early group being symptomatic for <or=3 months and the late group for >3 months. Surgical time, blood loss, severity of back pain, leg pain and numbness (visual analogue scale, or VAS), and a patient-oriented evaluation score (Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, or JOABPEQ) before and after surgery were compared. The JOABPEQ is a new evaluation method for lumbar spinal disorders based on Roland-Morris disability questionnaires and Short Form 36. There were 23 patients in each group. No significant differences were found between the groups in patients' demographics (age, sex, type of herniation), surgical time, blood loss, or pre- and postoperative VAS (lower-back pain, leg pain, numbness). There were no significant differences between the groups in the scores for the five subscales - pain-related disorders, gait disturbance, lumbar spine dysfunction, social life disturbance, psychological disorders - of the preoperative JOABPEQ. Postoperative scores for psychological disorders improved significantly (P < 0.05) in the late group (mean score 39.9) compared to the early group (mean score 22.1). Interestingly, no significant difference of improvement in the scores other than psychological disorder was found between the two groups. Early surgical intervention did not result in greater improvement of clinical outcomes for patients with lumbar disc herniation. Later surgical intervention resulted in significant improvement of psychological disorders.
    Journal of Orthopaedic Science 05/2010; 15(3):294-8. · 0.96 Impact Factor
  • Osteoarthritis and Cartilage 01/2010; 18. · 4.26 Impact Factor
  • Osteoarthritis and Cartilage 01/2010; 18. · 4.26 Impact Factor
  • Osteoarthritis and Cartilage 01/2010; 18. · 4.26 Impact Factor