Takuya Naraoka

Tumor-necrosis factor-α induces retinoic acid-inducible gene-I in rheumatoid fibroblast-like synoviocytes

Tumor-necrosis factor-alpha (TNF-alpha) is a potent proinflammtory cytokine and a key molecule in the pathogenesis of rheumatoid arthritis (RA). Retinoic acid-inducible gene-I (RIG-I) is a DExH box protein, which is known to play a role in the inflammatory and immune reactions. We previously reported about potential involvement of RIG-I in synovial inflammation in RA. In the present study, we demonstrated the expression of RIG-I in fibroblast-like synoviocytes stimulated with TNF-alpha. RNA interference against interferon (IFN)-beta abolished the TNF-alpha-induced RIG-I expression. In addition, knockdown of RIG-I partially inhibited the TNF-alpha-induced expression of CC chemokine ligand (CCL) 5, a chemokine with chemotactic activity toward lymphocytes and monocytes. These findings suggest that the TNF-alpha/IFN-beta/RIG-I/CCL5 pathway may be involved in the pathogenesis of synovial inflammation in RA.

Time-dependent gene expression and immunohistochemical analysis of the injured anterior cruciate ligament

Objectives This study aimed to investigate time-dependent gene expression of injured human anterior cruciate ligament (ACL), and to evaluate the histological changes of the ACL remnant in terms of cellular characterisation. Methods Injured human ACL tissues were harvested from 105 patients undergoing primary ACL reconstruction and divided into four phases based on the period from injury to surgery. Phase I was < three weeks, phase II was three to eight weeks, phase III was eight to 20 weeks, and phase IV was ≥ 21 weeks. Gene expressions of these tissues were analysed in each phase by quantitative real-time polymerase chain reaction using selected markers (collagen types 1 and 3, biglycan, decorin, α-smooth muscle actin, IL-6, TGF-β1, MMP-1, MMP-2 and TIMP-1). Immunohistochemical staining was also performed using primary antibodies against CD68, CD55, Stat3 and phosphorylated-Stat3 (P-Stat3). Results Expression of IL-6 was mainly seen in phases I, II and III, collagen type 1 in phase II, MMP-1, 2 in phase III, and decorin, TGF-β1 and α-smooth muscle actin in phase IV. Histologically, degradation and scar formation were seen in the ACL remnant after phase III. The numbers of CD55 and P-Stat3 positive cells were elevated from phase II to phase III. Conclusions Elevated cell numbers including P-Stat3 positive cells were not related to collagens but to MMPs’ expressions.

Periodic knee injections of collagen tripeptide delay cartilage degeneration in rabbit experimental osteoarthritis

IntroductionCollagen peptides have been reported to possess various biological activities for various cell types. The purposes of this study were, first, to examine the therapeutic effects of collagen tripeptide (Ctp) in rabbit osteoarthritis and, second, to explore a synergetic effect with hyaluronan (HA).MethodsOsteoarthritis was induced by anterior cruciate ligament transection of the right knee in 72 Japanese white rabbits and they were divided into four groups (control, Ctp, HA and Ctp/HA). Each material was injected weekly into the knee, and knee joint samples were collected 5, 10 and 15 weeks after surgery. Macroscopic and histomorphological analyses of cartilage were conducted. Expression of type II collagen and matrix metalloproteinase-13 was also analyzed immunohistochemically. A Tukeys honestly significant difference test was used to evaluate the statistical significance of difference in the macroscopic, histological and immnohistochemical results.ResultsAll treatment groups exhibited slightly higher resistance to the progression of osteoarthritis than the control group macroscopically 15 weeks after surgery. Histologically, intra-articular injection of Ctp significantly reduced cartilage degradation 10 weeks after surgery, and Ctp/HA significantly reduced it 5 weeks after surgery in comparison with the control. Immunohistochemically, both Ctp-treated and Ctp/HA-treated groups had significantly increased type II collagen-positive chondrocytes at the fifth week after the surgery, although the numbers of matrix metalloproteinase-13-positive chondrocytes were not affected.ConclusionPeriodical injections of Ctp and Ctp/HA delayed progression of cartilage degeneration of early osteoarthritis induced by anterior cruciate ligament transection in rabbits. This effect appears to be exerted by promotion of type II collagen synthesis predominantly.

Is Remnant Preservation Truly Beneficial to Anterior Cruciate Ligament Reconstruction Healing? Clinical and Magnetic Resonance Imaging Evaluations of Remnant-Preserved Reconstruction

Background: Remnant-preserved anterior cruciate ligament (ACL) reconstruction was introduced to improve clinical outcomes and biological healing. However, the effects of remnant preservation and the influence of the delay from injury until reconstruction on the outcomes of this technique are still uncertain. Purpose/Hypothesis: The purposes of this study were to evaluate whether remnant preservation improved the clinical outcomes and graft incorporation of ACL reconstruction and to examine the influence of the delay between ACL injury and reconstruction on the usefulness of remnant preservation. We hypothesized that remnant preservation improves clinical results and accelerates graft incorporation and that its effect is dependent on the delay between ACL injury and reconstruction. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 151 consecutive patients who underwent double-bundle ACL reconstruction using a semitendinosus graft were enrolled in this study: 74 knees underwent ACL reconstruction without a remnant (or the remnant was <25% of the intra-articular portion of the graft; NR group), while 77 knees underwent ACL reconstruction with remnant preservation (RP group). These were divided into 4 subgroups based on the time from injury to surgery: phase 1 was <3 weeks (n = 24), phase 2 was 3 to less than 8 weeks (n = 70), phase 3 was 8 to 20 weeks (n = 32), and phase 4 was >20 weeks (n = 25). Clinical measurements, including KT-1000 arthrometer side-to-side anterior tibial translation measurements, were assessed at 3, 6, 12, and 24 months after reconstruction. Magnetic resonance imaging evaluations of graft maturation and graft-tunnel integration of the anteromedial and posterolateral bundles were assessed at 3, 6, and 12 months after reconstruction. Results: There was no difference in side-to-side anterior tibial translation between the NR and RP groups. There was also no difference in graft maturation between the 2 groups. Furthermore, the time from ACL injury until reconstruction did not affect graft maturation, except in the case of very long delays before reconstruction (phase 4). Graft-tunnel integration was significantly increased in both groups in a time-dependent manner. However, there was no difference between the NR and RP groups. Conclusion: Remnant preservation did not improve knee stability at 2 years after ACL reconstruction. Furthermore, remnant preservation did not accelerate graft incorporation, especially during the acute and subacute injury phases.

Hyaluronic acid induces the release of growth factors from platelet-rich plasma

Background/Objective Platelet-rich plasma (PRP) and hyaluronic acid (HA) injection are both therapeutic options for osteoarthritis and chronic tendinopathy. Although several comparative studies on the two have been published, the effects of mixing PRP and HA are not fully understood. The purpose of this study is to investigate the influence of HA on platelets in PRP by measuring releasing growth factors. Methods PRP was produced from nine healthy adult volunteers (mean age, 32.8 ± 2.9 years; range, 29–37) with a commercial separation system. HA of weight-average molecular weight of 50–120 kDa was used. PRP group (PRP 1 mL + phosphate buffered saline 0.2 mL) and PRP + HA group (PRP 1 mL + HA 0.2 mL) were incubated at 37°C for 2 hours. The amounts of transforming growth factor β1 (TGF-β1) and platelet-derived growth factor (PDGF-AA) released from the PRP and PRP + HA samples were measured on Day 0, Day 3, and Day 5. In addition, the same growth factors on Day 5 were measured for PRP + high HA group (PRP 1 mL + HA 0.6 mL) with five donors. After collecting all of the samples on Day 5, the remaining gels were observed with Giemsa stain. Statistical analyses were performed using paired t tests to compare the PRP and HA groups at each time point, and a one-way analysis of variance (one-way ANOVA) with Tukey post hoc tests was used to compare the PRP, PRP + HA, and PRP + high HA groups. Results The TGF-β1 concentrations in the PRP and PRP + HA were 24.3 ± 7.2 μg/mL and 22.4 ± 1.8 μg/mL (p = 0.689) on Day 0, 17.2 ± 13.9 μg/mL and 25.4 ± 7.1 μg/mL (p = 0.331) on Day 3, and 12.7 ± 10.5 μg/mL and 33.7 ± 8.3 μg/mL (p = 0.034) on Day 5. The TGF-β1 concentrations on Day 5 were 24.1 ± 5.2 μg/mL (PRP group), 28.3 ± 2.4 μg/mL (PRP + HA), and 31.9 ± 4.8 μg/mL (PRP + high HA; one-way ANOVA: p = 0.003; post hoc PRP vs. PRP + HA: p = 0.016). The PDGF-AA concentrations in the PRP and PRP + HA groups were 2.30 ± 1.21 μg/mL and 2.32 ± 0.79 μg/mL (p = 0.931) on Day 0, 2.03 ± 0.53 μg/mL and 2.13 ± 0.73 μg/mL (p = 0.500) on Day 3, and 1.51 ± 0.40 μg/mL and 2.00 ± 0.52 μg/mL (p = 0.003) on Day 5. The PDGF-AA concentrations were 1.48 ± 0.46 μg/mL (PRP group), 1.94 ± 0.57 μg/mL (PRP + HA), and 2.69 ± 0.70 μg/mL (PRP + high HA; one-way ANOVA: p = 0.0002; PRP vs. PRP + high HA: p = 0.002; PRP + HA vs. PRP + high HA: p = 0.011) on Day 5. The PRP showed larger coagulated masses than the PRP + HA. The high concentration HA group had the smallest coagulated mass of all of the group. Conclusion The levels of growth factors released by PRP on Day 5 were increased by the addition of HA. A mixture of PRP and HA may be a more effective therapy than PRP or HA alone for osteoarthritis and tendinopathy.

Characteristics of elongated and ruptured anterior cruciate ligament grafts: An analysis of 21 consecutive revision cases

Background/objective Anterior cruciate ligament (ACL) reconstructions often fail without graft rupture. The purpose of this study was to compare the characteristics of patients with elongated and ruptured bone-patellar tendon-bone (BTB) grafts that required revision surgery. Methods Twenty one patients who required revisions of a BTB-reconstructed ACL between 2010 and 2015 were enrolled in this study. All patients were evaluated for bone tunnel position using computed tomography. Tunnel angle was calculated with radiographs. Stability under anaesthesia, and meniscus and cartilage condition were evaluated during the revision surgery. Age at primary surgery, time between primary and revision surgery, activity level, original tunnel position of the graft, and meniscus and cartilage condition were compared between elongated and ruptured grafts. Results Age at primary surgery was not significantly different between the two groups (p = 0.528). Time between primary and revision surgery as well as activity level were also not significantly different between the two groups (p = 0.010 and p = 0.307, respectively). Femoral bone tunnel position was more proximal (p = 0.003), and radiographic tunnel angle was not significantly different between the two groups (p = 0.029). The rupture group was significantly more unstable on the pivot shift (p < 0.003). Meniscus degeneration, meniscus tear, and cartilage damage were not significantly different between the two groups (p = 0.030, p = 0.311, and p = 0.505, respectively). Conclusion The location of the original femoral tunnel was more proximal in patients with elongated grafts than in those with ruptured grafts. Different bone tunnel position from native ACL might lead to graft elongation.

Quantitative analysis of dynamic patellar tracking in patients with lateral patellar instability using a simple video system

BACKGROUND As patellar dislocation occurs during activity, it is more important to assess the behavior of the patellofemoral joint under dynamic conditions. The aim of this study was to compare patellar tracking between knees with and without patellar dislocation in patients with an unstable patella and healthy controls using a simple video technique. METHODS Twenty-three knees with patellar dislocation (dislocated group), 23 contralateral knees without dislocation (non-dislocated group), and 23 healthy knees (control group) were examined. Those with skin markers on anatomical landmarks were made to extend their knees actively, and skin markers were attached to the examiners fingertips and the patella was followed by pinching. The knee during active knee extension was recorded with digital video cameras. The patella was tracked on imaging software, and the mediolateral patellar position (% patellar position: %PP) was calculated in reference to the knee width consecutively. RESULTS %PP was significantly different between the dislocated and control groups, from 30° (mean±SD: 58.9±6.2%, 54.6±4.7%) to 5° (64.2±5.2%, 55.2±5.2%). It was also significantly different between the non-dislocated and control groups, from 25° (58.9±7.1%, 54.5±4.6%) to 5° (63.8±6.5%, 55.2±5.2%). No significant difference in %PP was found between the dislocated and non-dislocated groups. CONCLUSION With the new video system, patellar tracking during active knee extension was successfully quantified. The tracking patterns were the same in knees with and without patellar dislocation, and the tracking in patients significantly differed from that in the controls at lower knee flexion angles. CLINICAL RELEVANCE The development of a quantitative examination technique for dynamic patellar tracking, which is easy to use and repeatedly applicable in a clinical situation, could help to follow-up the time-dependent changes and analyze the treatment effect on an unstable patella.

Does Remnant Preservation Influence Tibial Tunnel Enlargement or Graft-to-Bone Integration After Double-Bundle Anterior Cruciate Ligament Reconstruction Using Hamstring Autografts and Suspensory Fixation? A Computed Tomography and Magnetic Resonance Imaging Evaluation

Background: Remnant-preserving anterior cruciate ligament (ACL) reconstruction was introduced to improve clinical outcomes and biological healing. However, the influences of remnant preservation on tibial tunnel position and enlargement are still uncertain. Purpose: To evaluate whether remnant-preserving ACL reconstruction influences tibial tunnel position or enlargement and to examine the relationship between tunnel enlargement and graft-to-bone integration in the tibial tunnel. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 91 knees with double-bundle ACL reconstructions were enrolled in this study. ACL reconstruction was performed without a remnant (<25% of the intra-articular portion of the graft) in 44 knees (nonremnant [NR] group) and with remnant preservation in the remaining 47 knees (remnant-preserving [RP] group). Tibial tunnel position and enlargement were assessed using computed tomography (CT). Comparisons between groups were performed. Furthermore, graft-to-bone integration in the tibial tunnel was evaluated using magnetic resonance imaging, and the relationship between tunnel enlargement and graft-to-bone integration at 1 year after ACL reconstruction was assessed. Results: A total of 48 knees (25 in NR group, 23 in RP group) were included; 19 and 24 knees in the NR and RP groups were excluded, respectively, because of graft reruptures and a lack of CT scans. There were no significant between-group differences in tibial tunnel position (P > .05). The degree of posterolateral tunnel enlargement in the axial plane was significantly higher in the RP group than that in the NR group (P = .007) 1 year after ACL reconstruction. The degree of anteromedial tunnel enlargement on axial CT was significantly smaller in knees with graft-to-bone integration than in those without integration (P = .002) 1 year after ACL reconstruction. Conclusion: ACL reconstruction with remnant preservation did not influence tibial tunnel position and did not decrease the degree or incidence of tibial tunnel enlargement. At 1 year postoperatively, tunnel enlargement did not affect graft-to-bone integration in the posterolateral tunnel, but graft-to-bone integration was delayed in the anteromedial tunnel.

Greater Laxity in the Anterior Cruciate Ligament–Injured Knee Carries a Higher Risk of Postreconstruction Pivot Shift: Intraoperative Measurements With a Navigation System

Background: The presence of pivot shift after anterior cruciate ligament (ACL) reconstruction is correlated with worse clinical outcomes. An orthopaedic navigation system is a useful tool for quantifying laxity in the ACL-deficient knee. Purpose: To investigate the relationship between preoperative knee laxity measured by a navigation system and postoperative pivot shift (PPS) after ACL reconstruction. Study Design: Case-control study; Level of evidence, 3. Methods: One hundred patients who underwent primary ACL reconstruction (62 hamstring tendon grafts, 38 patellar tendon grafts) were grouped according to the presence or absence of pivot shift at the 2-year follow-up, and the groups were compared retrospectively. Before surgery, knee laxity was assessed with a navigation system to quantify posterior tibial reduction (PTR) during pivot-shift tests and anterior tibial translation (ATT) during Lachman tests. PTR and ATT cutoff values were determined by receiver operator characteristic (ROC) analysis. Results: Preoperative PTR and ATT were significantly larger for patients with PPS (PPS-positive group) than those without (PPS-negative group). In the ROC analysis, the PTR had an area under the curve of 0.871 (95% CI, 0.763-0.979; P < .0001) for predicting a PPS; this was larger than that obtained for the ATT, which had an area under the curve of 0.825 (95% CI, 0.705-0.946; P = .001). Because the ROC curve of the ATT had 2 peaks, the ATT alone was not a suitable predictor for PPS. Based on the ROC curve, the optimal PTR cutoff value was 7 mm, with 88.9% sensitivity and 71.4% specificity for PPS (adjusted odds ratio = 19.7; 95% CI, 2.1-187.9; P = .009). Setting the cutoff value as a combination of the PTR (≧7 mm) and ATT (≧12 mm) improved the specificity (88.9% sensitivity and 84.6% specificity; adjusted odds ratio = 149.8; 95% CI, 5.9-3822.7; P = .002) over that with the PTR alone. Conclusion: ACL injuries in knees with a large PTR had a higher risk of PPS. When reconstructing the ACL in a knee with a high degree of laxity, surgeons may need to adopt strategies to prevent PPS.

MECHANISMS OF ANTERIOR CRUCIATE LIGAMENT INJURIES IN VOLLEYBALL

Background Knee injuries were common in volleyball players, and ACL injury is a serious injury for athletes. Objective The purpose of this study was to investigate the mechanism of ACL injury in volleyball players using a questionnaire. Design Research study using a questionnaire. Setting Volleyball players who had ACL reconstruction at our institution. Patients Twenty-five females and 1 male (mean age; 24.6±11.0 years-old) volleyball players who ruptured their ACL during volleyball and underwent ACL reconstruction. Assessment of Risk Factors They were asked about their position, dominant hand defined as the spiking hand, side of injury, event during which the injury occurred (game or practice), the circumstance of injury (the situation in which the injury occurred, the specific motion at the time of injury) and player position and court location where the injury occurred. Results There were 19 wing spikers (left 13, right 6). Twenty-four players were right-handed and 2 players were left-handed, and 23 players injured the knees opposite to dominant hand. The 65.4% of injuries were prevalent during game. Twenty players (76.9%) were injured during spiking. Twenty-one players (80.8%) receive injured during landing, and 16 of them injured with single-leg landing after spiking. Most of ACL injuries (84.6%) occurred in front of the attack line near the net. Conclusions Single leg landing after spiking close to the net was the most common cause of injury, and most of wing spikers injured the knee opposite to their dominant hand. It suggests that wing spikers need to consider prevention strategies focusing on spiking movement.