山口 智志

Matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) are thought to play critical roles in cartilage degradation at the early phase of osteoarthritis (OA). The aim of this study is to examine the effect of chemically modified Mmp13 or Adamts5 small interfering RNA (siRNA), alone or in combination, in a mouse OA model. OA pathology was surgically induced in 9-week-old male C57/BL6 mice (n = 64) via destabilization of the medial meniscus (DMM). We used chemically modified siRNA (Accell siRNAs®) for Mmp13 and Adamts5, as well as a non-targeting control and evaluated their combined and individual effects after injection in the DMM model. The control group (n = 16) was injected with non-targeting siRNA and the normal group (n = 16) did not undergo any surgical induction or intra-articular injection. Histological assessment of the articular cartilage was conducted at 4 and 8 weeks post-DMM surgery to evaluate OA progression. Significant improvement in the histological score was observed at 8 weeks after DMM in all three siRNA-treated groups compared to the control siRNA-injected group. The score of the combined group was significantly lower than that of the Adamts5 siRNA-only group. No significant differences were noted between the Mmp13 siRNA-only group and the combined group. Combined intra-articular injection of Mmp13 and Adamts5 siRNA resulted in almost the same inhibitory effects as Mmp13 siRNA alone on cartilage degradation at the early phase of OA.

Purpose To determine the time-dependent change in strain ratios (SRs) at the healing site of an Achilles tendon rupture in a rabbit model of tendon transection and to assess the correlation between SRs and the mechanical and histologic properties of the healing tissue. Materials and Methods Experimental methods were approved by the institutional animal care and use committee. The Achilles tendons of 24 New Zealand white rabbits (48 limbs) were surgically transected. The SRs of Achilles tendons were calculated by using compression-based quantitative ultrasonographic elastography measurements obtained 2, 4, 8, and 12 weeks after transection. After in vivo elastography, the left Achilles tendon was harvested for mechanical testing of ultimate load, ultimate stress, elastic modulus, and linear stiffness, and the right tendons were harvested for tissue histologic analysis with the Bonar scale. Time-dependent changes in SRs, mechanical parameters, and Bonar scale scores were evaluated by using repeated-measures analysis of variance. The correlation between SRs and each measured variable was evaluated by using the Spearman rank correlation coefficient. Results Mean SRs and Bonar scale values decreased as a function of time after transection, whereas mechanical parameters increased (P < .001). SR correlated with ultimate stress (ρ = 0.68, P <.001,) elastic modulus (ρ = 0.74, P <.001), and the Bonar scale (ρ = 0.87, P <.001). Conclusion Quantitative elastography could be a useful method with which to evaluate mechanical and histologic properties of the healing tendon. © RSNA, 2017 Online supplemental material is available for this article.

AIMS: The purposes of this study were to clarify first, the incidence of peroneal tendon dislocation in patients with a fracture of the talus and second the factors associated with peroneal tendon dislocation. PATIENTS AND METHODS: We retrospectively examined 30 patients (30 ankles) with a mean age of 37.5 years, who had undergone internal fixation for a fracture of the talus. Independent examiners assessed for peroneal tendon dislocation using the pre-operative CT images. The medical records were also reviewed for the presence of peroneal tendon dislocation. The associations between the presence of dislocation with the patient characteristics or radiological findings, including age, mechanism of injury, severity of fracture, and fleck sign, were assessed using Fisher's exact tests. RESULTS: The pre-operative CT images showed peroneal tendon dislocation in eight out of 30 patients. Dislocation was found later in one patient whose pre-operative CT image had not shown dislocation. The overall incidence of peroneal tendon dislocation was 30% (9/30). The presence of dislocation was associated with the presence of a fleck sign (p = 0.03). CONCLUSIONS: Surprisingly, approximately one-third of the patients who underwent internal fixation for a fracture of the talus had peroneal tendon dislocation. This was associated with a fleck sign. Cite this article: Bone Joint J 2017;99-B:489-93.

OBJECTIVES: The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation in vitro and to determine whether pre-microfracture systemic administration of G-CSF (a bone marrow stimulant) could improve the quality of repaired tissue of a full-thickness cartilage defect in a rabbit model. METHODS: MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium.A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically. RESULTS: The cell count in the low-dose G-CSF medium was significantly higher than that in the control medium. The differentiation potential of MSCs was preserved after culturing them with G-CSF.Macroscopically, defects were filled and surfaces were smoother in the G-CSF groups than in the control group at four weeks. At 12 weeks, the quality of repaired cartilage improved further, and defects were almost completely filled in all groups. Microscopically, at four weeks, defects were partially filled with hyaline-like cartilage in the G-CSF groups. At 12 weeks, defects were repaired with hyaline-like cartilage in all groups. CONCLUSIONS: G-CSF promoted proliferation of MSCs in vitro. The systemic administration of G-CSF promoted the repair of damaged cartilage possibly through increasing the number of MSCs in a rabbit model.Cite this article: T. Sasaki, R. Akagi, Y. Akatsu, T. Fukawa, H. Hoshi, Y. Yamamoto, T. Enomoto, Y. Sato, R. Nakagawa, K. Takahashi, S. Yamaguchi, T. Sasho. The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair. Bone Joint Res 2017;6:123-131. DOI: 10.1302/2046-3758.63.BJR-2016-0083.

Magnetic resonance imaging (MRI) can be used to identify most types of meniscal tears; however, meniscocapsular separation of the medial meniscus can be difficult to identify with MRI. Here we present a technical note on the intrasurgical use of ultrasonography for the detection of meniscocapsular separation and confirmation of the beneficial effect of suturing on the stability of this lesion in a representative case of meniscocapsular separation that could be diagnosed with ultrasonography but not MRI preoperatively. Ultrasonography can detect meniscocapsular separation as a vertical low echoic area and be performed together with arthroscopy using the picture-in-picture function of the ultrasonography machine. Ultrasonography is an effective tool for diagnosing meniscocapsular separation and is helpful during arthroscopic surgery.

Bipartite navicular bone is an uncommon condition that can cause midfoot pain in children and adolescents. No treatment methods, other than conservative management, have been reported. We report the cases of 2 adolescent soccer players who underwent internal fixation of the painful bipartite fragments, resulting in nonunion. After failure of conservative management, the patients underwent surgery. Curettage of the junction between the 2 bone fragments was performed, and autologous cancellous bone was grafted. Next, the fragments were fixed with variable-threaded screws. Bone union of the bipartite fragments was once achieved on computed tomography in both cases at 3 and 5 months after surgery, respectively. However, separation of the fragment occurred in both cases after the patients had returned to sports. Although the patients were able to return to sports activities, they still had mild midfoot pain 3 and 2 years after surgery, respectively. Internal fixation using screws and an autologous bone graft for painful bipartite navicular bone in adolescent athletes is not recommended, and other surgeries should be considered to achieve bony union.

BACKGROUND: The purposes of this study were to compare the quality of life (QOL) of subjects who had untreated symptomatic hallux valgus with the QOL of the general population and to investigate factors associated with the QOL of the subjects. METHODS: One hundred sixteen subjects with previously untreated and symptomatic hallux valgus were surveyed. QOL was assessed using the 36-item Short Form Health Survey (SF-36). Additionally, clinical evaluations (the visual analog scale for pain, Japanese Society for Surgery of the Foot Scale, lesser toe pain, and pain in other parts of the body) and radiographic evaluations (hallux valgus angle, intermetatarsal angle between the first and second metatarsals, and dislocation of the second metatarsophalangeal joint) were performed. Differences in the SF-36 between the subjects and the general population were tested using independent t tests. Correlations between the QOL measurements, clinical evaluations, and radiographic evaluations were assessed using Spearman rank correlation coefficient. RESULTS: All SF-36 subscales and physical component summary scores for the subjects were significantly lower than those of the general population. Notably, the standardized physical function subscale (38.2 ± 15.8, P < .001) and physical component summary scores (38.9 ± 14.5, P < .001) were more than 10 points lower than those of the general population. Most QOL and clinical evaluation parameters were not correlated or were negligibly correlated with radiographic evaluations. Similarly, lesser toe pain or pain in other parts of the body was not correlated with QOL or clinical evaluations. CONCLUSION: The QOL of untreated and symptomatic hallux valgus subjects was lower than that of the general population. All QOL and clinical evaluation parameters were not significantly or negligibly correlated with the severity of toe deformities. Surgical decision making should not be based on the severity of the deformity alone, but rather patient QOL should also be carefully assessed. LEVEL OF EVIDENCE: Level III, comparative series.

INTRODUCTION: To evaluate time-dependent changes in the syndesmotic reduction after syndesmotic screw fixation and one year after screw removal for ankle malleolar fractures, and to assess whether the incidence of syndesmotic malreduction changes depending on the measurement method. METHODS: We assessed twenty patients who underwent syndesmotic screw fixation for ankle fractures. The syndesmotic screws were removed after six weeks of the fracture surgery. Syndesmotic reduction was assessed within two weeks of the fracture surgery and one year after the screw removal using the axial computer tomographic images. Side-to-side differences in the anterior and posterior tibiofibular distances, anteroposterior fibular translation, and fibular rotation were measured. RESULTS: The mean anterior tibiofibular distance was 0.7mm after syndesmotic fixation. It increased to 1.9mm at one year after screw removal (p=0.002). After syndesmotic fixation, four ankles had malreduction of the anterior tibiofibular distance, including three ankles with widening and one with overtightening. At one year, eight ankles had malreduction, all of whom had widening. The other measurement values did not change over time (0.1mm vs. 0.6mm for the posterior tibiofibular distance, 0.2mm vs. 0.3mm for the anteroposterior fibular translation, and 0.7° vs. 0° for the fibular rotation). The incidences of malreduction were significantly different depending on the definition of malreduction, ranging from 10% to 50% after syndesmotic fixation (p=0.01) and from 20% to 60% at one year after screw removal (p=0.02). CONCLUSIONS: The anterior tibiofibular distance widened after one year of syndesmotic screw removal. The incidence of malreduction varied depending on the measurement method.

PURPOSE: Our previous study showed that partial-thickness articular cartilage defects (PTCDs) created in immature rats spontaneously healed to resemble normal hyaline cartilage, but that of mature rats did not. To identify molecules involved in the spontaneous cartilage repair observed in this model, gene expression was compared between PTCD and sham-operated cartilage of immature and mature rats. MATERIALS AND METHODS: Six sets of gene comparisons were made at 12, 24, and 48 hours after the creation of PTCDs in immature and mature rats using microarrays. All the genes upregulated in immature cartilage at 12 hours were selected for further analysis if their expression pattern was not irregular such that diminished at 24 hours and re-upregulated at 48 hours. Relationships among genes selected through the above steps were analyzed using Ingenuity Pathway Analysis (IPA) software. After deriving networks, important molecules were further narrowed down by location within a network. Genes were regarded as central if they had relationships with more than 10 molecules in a network. Protein localization in tissues was confirmed by immunohistochemistry. RESULTS: Five networks were identified. Their functional annotations were gene expression, cell cycle, growth and proliferation, and cell signaling. Transforming growth factor-beta (TGF-β) was centrally located in the network with the highest IPA score and mothers against decapentaplegic homolog-3 (Smad3) were centrally located in the second highest ranking network. Phosphorylated Smad3 was detected in the nuclei of chondrocytes in immature cartilage. CONCLUSIONS: Our data suggest the possible importance of Smad3 in the TGF-β signaling in the spontaneous healing of PTCDs in immature rats.

Intratendinous ganglion cysts are rare lesions of unknown etiology that originate within a tendon. We report the case of a 34-year-old female with an intratendinous ganglion in the plantar portion of the flexor hallucis longus tendon. The intratendinous ganglion recurred after ultrasound-guided needle aspiration. Tendoscopic excision of the intratendinous ganglion cyst achieved a satisfactorily result without recurrence.

OBJECTIVES: The purposes of this study were to measure intraobserver and interobserver repeatability of quantitative elastography using an acoustic coupler for the Achilles tendon, to compare elastographic values among different age groups, and to assess the correlation between quantitative and conventional qualitative measurements. METHODS: One hundred asymptomatic Achilles tendons of 50 volunteers were examined. For quantitative elastography, the strain value of the tendon was divided by that of the acoustic coupler with a known Young modulus, and the strain ratio was calculated. B-mode image assessment and qualitative elastography were also performed. Intraobserver repeatability and interobserver repeatability of strain ratio measurements were calculated. The strain ratios were compared among age groups by the Kruskal-Wallis test. Additionally, strain ratios for each B-mode grade and qualitative elastographic grade were compared by the Wilcoxon signed rank test. RESULTS: Intraobserver repeatability intraclass correlation coefficient (1, 3) values were 0.87 and 0.93, respectively. The correlation coefficient between the observers' measurements was 0.61. The strain ratio for the 30s age group was 0.27, which was significantly lower than the values for the other age groups (P < .001). Although 97 of 100 tendons were normal on B-mode evaluations, 36 of the 97 tendons were degenerated on qualitative elastography and also had higher strain ratio values than normal tendons. CONCLUSIONS: Quantitative elastography using an acoustic coupler is a reproducible technique for measuring the elasticity of the Achilles tendon. It may detect early tendon degeneration that is not depicted on B-mode imaging.

Background: Alteration in shoulder kinematics has been suggested as one cause of symptoms in shoulders with rotator cuff tears (RCTs). However, only a few studies comparing symptomatic and asymptomatic RCTs using kinematic analysis have been performed. The purpose of this study was to compare 3-dimensional (3D) scapular and glenohumeral kinematics during scapular-plane abduction among symptomatic RCTs, asymptomatic RCTs, and healthy shoulders. Methods: This study included 7 healthy shoulders in subjects with a mean age of 62 years, 5 symptomatic RCTs in subjects with a mean age of 70 years, and 7 asymptomatic RCTs in subjects with a mean age of 67 years. All shoulders with RCTs had medium-sized tears (1-3 cm in the coronal plane) that were confirmed with magnetic resonance imaging. Biplane fluoroscopic images during scapular-plane abduction were recorded, and computed tomography-derived 3D bone models were matched with the silhouettes of the bones on the fluoroscopic images using 3D/2-dimensional model-image registration techniques. Angular values of the scapula and glenohumeral kinematics were compared among the 3 groups. Results: Posterior tilt of the scapula was significantly smaller in the symptomatic RCTs (3.1° ± 1.8°) than in healthy shoulders (10.4° ± 0.8°) (P = .049). The humerus of the symptomatic shoulders was less externally rotated relative to the scapula throughout the activity than the healthy shoulders and asymptomatic RCTs (P = .006 and P = .028 respectively). However, there were no kinematic differences between the asymptomatic RCTs and healthy shoulders. Conclusion: Kinematic changes in symptomatic RCTs might be associated with development of symptoms. Improvement of these kinematic changes may be a key to successful conservative treatment for symptomatic RCTs.

PURPOSE: To determine if magnetic resonance (MR) imaging T2 mapping can be used to quantify histologic tendon healing by using a rabbit Achilles tendon transection model treated with platelet-rich plasma (PRP). MATERIALS AND METHODS: Experiments were approved by the Institutional Animal Care and Use Committee. The Achilles tendons of 24 New Zealand white rabbits (48 limbs) were surgically transected, and PRP (in the test group) or saline (in the control group) was injected into the transection site. The rabbits were sacrificed 2, 4, 8, and 12 weeks after surgery. Thereafter, T2 mapping and histologic evaluations were performed by using the Bonar scale. A mixed-model multivariate analysis of variance was used to test the effects of time and PRP treatment on the T2 value and Bonar grade, respectively. The correlation between the T2 value and Bonar grade was also assessed by using the Spearman correlation coefficient. RESULTS: The Bonar scale values decreased in both groups during tendon healing. The T2 value also shortened over time (P < .001 for both groups). The T2 values were positively correlated with the Bonar grade (ρ = 0.78, P < .001). Both the T2 value and Bonar scale value were lower in the PRP group than in the control group at 4, 8, and 12 weeks; however, there was no significant effect of PRP treatment on the T2 value or Bonar grade. CONCLUSION: The T2 value changes reflected histologic tendon healing. While T2 and Bonar grade were lower at all time points in tendons treated with PRP, there was no significant difference between the treatment and control tendons.

BACKGROUND: Correction of pronation deformity and metatarsal primus varus is an important component of hallux valgus surgery, necessary to achieve a satisfactory correction and to prevent post-operative recurrence. Roundness of the lateral edge of the first metatarsal head (round sign) on the dorsoplantar radiograph of the foot has been empirically advocated as an indicator of first metatarsal pronation. The purpose of this study was to clarify the effect of rotation and inclination of the first metatarsal on the shape of the lateral edge of the first metatarsal head. METHODS: Computed tomographic images of feet in 30 subjects, without pathology of the first metatarsophalangeal joint, were included. Digitally reconstructed radiographs of the first metatarsal were created using the computed tomographic data. Thirty-nine images were created of each first metatarsal at different degrees of rotation (-10° to 30° of pronation) and inclination (-10° to 20° of plantarflexion). Then, the shape of the lateral edge of the first metatarsal head was classified into three types: angular, intermediate, and round. Generalized estimation equations were used to test if the shapes of the first metatarsal head were significantly different across the range of pronation and plantarflexion angles. RESULTS: The positive round sign changed to negative as the first metatarsal supinated. In most feet, these changes occurred as the pronation angle decreased from 10° to 0°. The positive round sign also changed to negative as the first metatarsal head plantarflexed. CONCLUSION: Positive round sign of the first metatarsal head on the dorsoplantar radiograph of the foot was significantly associated with increased pronation as well as decreased inclination of the first metatarsal. Negative round sign may be used as an indicator of effective correction of first metatarsal pronation during hallux valgus surgery.

BACKGROUND: Imaging is of great importance in diagnosing meniscal tears. The aim of this study was to assess the accuracy of high-resolution ultrasound in the diagnosis of meniscal tears, with arthroscopic examination as the standard reference, after resolution was confirmed with a target-mounted reference phantom. An additional goal was to elucidate the area of the meniscus that could be visualized with the same ultrasound machine after placement of markers into the menisci of cadaveric knees. METHODS: Seventy patients were included for the assessment of the accuracy of a high-resolution ultrasound machine with a 14.0 to 6.0-MHz linear transducer. The preoperative ultrasound diagnosis, in terms of the presence and type of tear, was compared with that in the surgical reports. In the cadaveric studies, nine needles were placed in the peripheral zone of the menisci at regular intervals and the number of needles that could be observed with the system was recorded. RESULTS: The overall sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound examination for meniscal tears were 88%, 85%, 85%, and 88%, respectively. These statistical parameters did not differ significantly between the medial and lateral menisci. The sensitivity for diagnosing horizontal, vertical, radial, flap, bucket-handle, and complex tears and for detecting discoid lateral menisci was 83%, 64%, 0%, 64%, 54%, 90%, and 80%, respectively. Ten percent of the lateral menisci could not be evaluated because of poor images. The cadaveric studies revealed that the ultrasound visualized the entire meniscus except for the anterior horn. CONCLUSIONS: The findings of this study suggest that ultrasound examination may be suitable for screening for meniscal tears. The fact that almost 10% of the lateral menisci could not be evaluated because of poor images appears to be a weakness of ultrasound.

OBJECTIVE: To examine whether the detection of osteophytes anywhere in the knee could serve as a pre-radiographic biomarker for osteoarthritis (OA) development. METHODS: Baseline magnetic resonance imaging (MRIs) of 132 participants in the Osteoarthritis Initiative (OAI) were studied. Based on radiographs, 66 knees were assessed as osteoarthritis-free (no-osteoarthritis [NOA], or Kellgren/Lawrence [K/L] severity grade 0/1 both at baseline and 48 months), and another 66 knees were assessed as having radiographic OA changes (pre-radiographic osteoarthritis [PROA], or with K/L grade 0/1 at baseline and grade ≥ 2 at 48 months). Using baseline MRI data, we examined eight sites of osteophyte formation: the medial and lateral femoral condyle (MFC and LFC, respectively); medial and lateral tibial plateau (MTP and LTP, respectively); medial and lateral facets of the patellofemoral joint (PM and PL, respectively); tibial spine (TS); and femoral intercondylar notch (IC). Knee joint osteophyte size was assessed via the 8-point marginal osteophytes item of the whole-organ magnetic resonance imaging score (WORMS). The frequencies and distributions of osteophytes were compared between groups. RESULTS: Mild-size osteophytes (defined as score ≥ 2) were observed more frequently at the MFC (P = 0.00278), MTP (P = 0.0046), TS (P = 0.0146), PM (P < 0.0001), PL (P = 0.0012), and IC (P < 0.0001) in PROA knees than in NOA knees. Moderate-size osteophytes (defined as score ≥ 4) were more frequently observed in PROA knees than in NOA knees only at the IC (P < 0.0001). CONCLUSION: Knees with osteophyte formation at the IC, even those of K/L severity grade 0/1, are at risk for the development of radiographic OA by 48 months.