Takahisa Sasho

Existence of a Neuropathic Pain Component in Patients with Osteoarthritis of the Knee

Purpose Pain from osteoarthritis (OA) is generally classified as nociceptive (inflammatory). Animal models of knee OA have shown that sensory nerve fibers innervating the knee are significantly damaged with destruction of subchondral bone junction, and induce neuropathic pain (NP). Our objective was to examine NP in the knees of OA patients using painDETECT (an NP questionnaire) and to evaluate the relationship between NP, pain intensity, and stage of OA. Materials and Methods Ninety-two knee OA patients were evaluated in this study. Pain scores using Visual Analogue Scales (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), painDETECT, duration of symptoms, severity of OA using the Kellgren-Lawrence (KL) system, and amount of joint fluid were evaluated and compared using a Spearmans correlation coefficient by rank test. Results Our study identified at least 5.4% of our knee OA patients as likely to have NP and 15.2% as possibly having NP. The painDETECT score was significantly correlated with the VAS and WOMAC pain severity. Compared with the painDETECT score, there was a tendency for positive correlation with the KL grade, and tendency for negative correlation with the existence and amount of joint fluid, but these correlations were not significant. Conclusion PainDETECT scores classified 5.4% of pain from knee OA as NP. NP tended to be seen in patients with less joint fluid and increased KL grade, both of which corresponded to late stages of OA. It is important to consider the existence of NP in the treatment of knee OA pain.

Correlation between MMP-13 and HDAC7 expression in human knee osteoarthritis

Recent studies suggest that histone deacetylase (HDAC) inhibitors may therapeutically prevent cartilage degradation in osteoarthritis (OA). Matrix metalloproteinase-13 (MMP-13) plays an important role in the pathogenesis of this disease and in the present study we investigated the correlation between HDACs and MMP-13. Comparing the expression of different HDACs in cartilage from OA patients and healthy donors, HDAC7 showed a significant elevation in cartilage from OA patients. High level of HDAC7 expression in OA cartilage was also confirmed by immunohistochemistry. Knockdown of HDAC7 by small interference RNA (siRNA) in SW1353 human chondrosarcoma cells strongly suppressed interleukin (IL)-1-dependent and independent induction of MMP-13 gene expression. In conclusion, elevated HDAC7 expression in human OA may contribute to cartilage degradation via promoting MMP-13 gene expression, suggesting the critical role of MMP-13 in OA pathogenesis.

In vivo 3-dimensional analysis of scapular kinematics: comparison of dominant and nondominant shoulders

BACKGROUND Alterations in scapular motion frequently are seen in association with various shoulder disorders. It is common clinically to compare the pathological shoulder with the contralateral shoulder, in spite of arm dominance, to characterize the disorder. However, there have been few articles that test the underlying assumption that dominant and nondominant shoulders exhibit comparable dynamic kinematics. The purpose of this study was to compare the 3-dimensional (3-D) scapular kinematics of dominant and nondominant shoulders during dynamic scapular plane elevation using 3-D-2-D (2-dimensional) registration techniques. MATERIALS AND METHODS Twelve healthy males with a mean age of 32 years (range, 27-36) were enrolled in this study. Bilateral fluoroscopic images during scapular plane elevation and lowering were taken, and CT-derived 3-D bone models were matched with the silhouette of the bones in the fluoroscopic images using 3-D-2-D registration techniques. Angular values of the scapula and scapulohumeral rhythm were compared between dominant and nondominant shoulders with statistical analysis. RESULTS There was a significant difference in upward rotation angles between paired shoulders (P < .001), while significant differences were not found in the other angular values and scapulohumeral rhythm. The dominant scapulae were 10° more downwardly rotated at rest and 4° more upwardly rotated during elevation compared to the nondominant scapulae. DISCUSSION/CONCLUSION Scapular motion was not the same between dominant and nondominant arms in healthy subjects. The dominant scapula was rotated further downward at rest and reached greater upward rotation with abduction. These differences should be considered in clinical assessment of shoulder pathology.

Dynamic In Vivo Glenohumeral Kinematics During Scapular Plane Abduction in Healthy Shoulders

STUDY DESIGN Controlled laboratory study. OBJECTIVES To measure superior/inferior translation and external rotation of the humerus relative to the scapula during scapular plane abduction using 3-D/2-D model image registration techniques. BACKGROUND Kinematic changes in the glenohumeral joint, including excessive superior translation of the humeral head and inadequate external rotation of the humerus, are believed to be a possible cause of shoulder impingement. Although many researchers have analyzed glenohumeral kinematics with various methods, few articles have assessed dynamic in vivo glenohumeral motion. METHODS Twelve healthy males with a mean age of 32 years (range, 27-36 years) were enrolled in this study. Fluoroscopic images of the dominant shoulder during scapular plane elevation were taken, and computed tomography-derived 3-D bone models were matched with the silhouette of the bones in the fluoroscopic images using 3-D/2-D model image registration techniques. The kinematics of the humerus relative to the scapula were determined using Euler angles. RESULTS On average, there was 2.1 mm of initial humeral translation in the superior direction from the starting position to 105° of humeral elevation. Subsequently, an average of 0.9 mm of translation in the inferior direction occurred between 105° and maximum arm elevation. The average amount of external rotation of the humerus was 14° from the starting position to 60° of humeral elevation. The humerus then rotated internally an average 9° by the time the shoulder reached maximum elevation. These changes in superior/inferior translation and external/internal rotation were statistically significant (P<.001 and P = .001, respectively), based on 1-way repeated-measures analysis of variance. CONCLUSION The observed glenohumeral translations and rotations characterize healthy shoulder function and serve as a preliminary foundation for quantifying pathomechanics in the presence of glenohumeral joint disorders.

Ankle and Subtalar Kinematics during Dorsiflexion-Plantarflexion Activities

Background: Understanding the effect of weightbearing on subtalar and ankle joint kinematics is critical for the diagnosis and treatment of foot disorders. However, dynamic in vivo kinematics of these joints are not well studied. The purpose of this study was to compare in vivo kinematics during nonweightbearing and weightbearing activities in healthy subjects. Methods: Seven healthy subjects with a mean age of 32 (range, 23 to 42) years were enrolled. Oblique lateral fluoroscopic images of nonweightbearing and weight-bearing dorsiflexion-plantarflexion activities were recorded. Three dimensional subtalar, ankle, and ankle-subtalar joint complex kinematics were determined using 3D-2D model registration techniques with 3D bone models and single-plane fluoroscopy. Results: During the weightbearing activity from 20 degrees dorsiflexion to 15 degrees plantarflexion, the subtalar joint was significantly more everted, dorsiflexed, and abducted, and the calcaneus showed a significantly more posterior position, than during the nonweightbearing activity. The ankle joint was significantly more plantarflexed and adducted during the weightbearing activity than the nonweightbearing activity. The ankle-subtalar joint complex was significantly more everted, and the calcaneus showed significantly greater posterior position than the nonweightbearing activity. Conclusion: These observations provide basic quantitative descriptions of weightbearing and nonweightbearing kinematics for healthy joints. Clinical Relevance: These data can serve as the basis for comparison with pathologic feet for both diagnostic and therapeutic purposes.

Effects of autologous platelet-rich plasma on cell viability and collagen synthesis in injured human anterior cruciate ligament.

BACKGROUND Platelet-rich plasma is a fraction of plasma in which platelets are concentrated. It is reported to represent a source of multiple growth factors that promote tissue repair. In anticipation of the eventual testing of platelet-rich plasma in anterior cruciate ligament (ACL)-deficient patients, we examined the effect of autologous platelet-rich plasma on human ACL cell function in vitro. METHODS Fresh blood and ACL remnants were obtained from four patients who underwent ACL reconstruction surgery. Platelet-poor plasma and platelet-rich plasma were prepared from the blood samples. The concentrations of various growth factors in each preparation were tested with use of enzyme-linked immunosorbent assays. Isolated ACL cells were cultured in the presence of 5% fetal bovine serum, 5% platelet-poor clot releasate, 5% platelet-rich clot releasate, or 10% platelet-rich clot releasate. Platelet-rich plasma and platelet-poor plasma releasates were applied to the ACL cells from the same patient autologously. Cell viability and collagen synthesis in each group were analyzed, and semiquantitative gene-expression assays for type-I and III collagen were also performed. RESULTS The concentrations of the main growth factors (transforming growth factor-beta, platelet-derived growth factor, epidermal growth factor, and vascular endothelial growth factor) were much higher in platelet-rich clot releasate than in platelet-poor clot releasate. In vitro treatment of ACL cells with platelet-rich clot releasate resulted in a significant increase in cell number compared with platelet-poor clot releasate. Total collagen production by the platelet-rich clot releasate-treated cells was significantly higher than that of the platelet-poor clot releasate-treated cells only because of enhanced cell proliferation. There was no significant effect of platelet-rich clot releasate treatment on gene expression for type-I collagen, but expression of type-III collagen was significantly enhanced by the treatment with platelet-rich clot releasate. CONCLUSIONS These results suggest that autologous platelet-rich plasma can enhance ACL cell viability and function in vitro.

Mechanical overloading causes mitochondrial superoxide and SOD2 imbalance in chondrocytes resulting in cartilage degeneration

Mechanical stress and aging are major risk factors of cartilage degeneration. Human studies have previously reported that oxidative damage increased, while SOD2 protein was reciprocally downregulated in osteoarthritic degenerated cartilage. However, it remains unclear whether mitochondrial superoxide imbalance in chondrocytes causes cartilage degeneration. We herein demonstrate that mechanical loading promoted mitochondrial superoxide generation and selective Sod2 downregulation in chondrocytes in vivo and that mitochondrial superoxide inducer also downregulated Sod2 expression in chondrocytes in vitro. A genetically manipulated model revealed that Sod2 deficiency in chondrocytes also resulted in mitochondrial superoxide overproduction and dysfunction, thus leading to cartilage degeneration. Intra-articular injection of a permeable antioxidant effectively suppressed the mechanical loading-induced mitochondrial superoxide generation and cartilage degeneration in mice. Our findings demonstrate that mitochondrial superoxide plays a pivotal role in the development and progression of osteoarthritis, and the mitochondrial superoxide balance may therefore be a promising target for the treatment of cartilage degeneration.

In vivo kinematics of anterior cruciate ligament deficient knees during pivot and squat activities

BACKGROUND Knee kinematics during pivoting activities are not well studied, but might provide insight critical to understanding the pathology of the anterior cruciate ligament deficient knee. The purpose of this study was to compare in vivo kinematics during weight bearing pivot and squat activities in patients with unilateral anterior cruciate ligament deficient knees, and to contrast those kinematics with the uninjured contralateral knees. METHODS Eight unilateral anterior cruciate ligament deficient patients with a mean age of 41 (SD 7) years were enrolled. Anterior cruciate injury was confirmed by positive Lachman test and MRI. Lateral fluoroscopic images of pivot and squat activities were recorded for both anterior cruciate ligament deficient and contralateral knees. Three-dimensional tibiofemoral kinematics and centers of rotation for each knee were determined using 3D-2D model registration techniques. FINDINGS During pivoting, the tibia of the anterior cruciate ligament deficient knee was significantly more anterior than the contralateral knee during tibial neutral to internal rotation. The pivot activity showed lateral centers of rotation in both anterior cruciate ligament deficient and contralateral knees while squatting showed medial centers of rotation. INTERPRETATION This dynamic method might be useful to objectively characterize restoration of dynamic function in knees with various types of anterior cruciate ligament reconstructions. These results also indicate kinematics during squatting type activities cannot be extrapolated to predict knee kinematics during pivoting types of activities.

Detection of pain-related molecules in the subchondral bone of osteoarthritic knees

Knee pain is predominant among osteoarthritis (OA) patients, but the mechanism is poorly understood. We investigated subchondral bone as a source of OA knee pain using immunohistochemistry. Fifteen medial-type OA knees with minimum involvement of the lateral compartment determined by X-ray as well as magnetic resonance imaging that received total knee arthroplasty (TKA) were involved. Each pair of the medial femoral condyle (MFC) and lateral femoral condyle (LFC) was compared obtained at the time of TKA. Osteocartilaginous MFC and LFC specimens were histologically examined and stained with antibodies against cyclooxygenase 1 (Cox-1), cyclooxygenase 2 (Cox-2), substance P, tumor necrosis factor-alpha (TNF-α), and neuron-specific class III beta-tubulin (TUJ1), a pan-neuronal marker. Formation of cystic lesions was more frequently seen in the MFC. The lesions were composed of vascular endothelial cells, osteoclasts, and mononuclear cells and were present in similar proportions between the MFC and the LFC. Four out of 15 MFC specimens were positive for Cox-1, 15 for Cox-2, and 13 for TNF-α. No LFC specimens were positive for any antibodies. Substance P-positive and TUJ1-positive fibers were found in the subchondral area of the MFC, but not in the LFC. Pathological changes in the subchondral bone can be a source of knee pain, which was detectable by the positive immunoreactivity of substance P, Cox-2, TNF-α, and TUJ1, in the subchondral bone of affected compartments. The relatively immediate reduction in pain obtained by TKA might account for the involvement of the subchondral bone in knee pain because most of the affected subchondral plate is excised in TKA (debridement effect of TKA).

Lateral Laxity in Flexion Increases the Postoperative Flexion Angle in Cruciate-Retaining Total Knee Arthroplasty

Thirty-eight patients diagnosed with osteoarthritis underwent 41 cruciate-retaining total knee arthroplasties. In varus and valgus tests at flexion, subjects were seated on a table at 80° of knee flexion; 50 N was applied perpendicular to the lower leg. The factors affecting the postoperative flexion angle were investigated in a multiregression analysis. The mean joint angles of the flexion-valgus and flexion-varus tests were 3.4° ± 1.4° and 6.2° ± 2.5°, respectively. The flexion-varus angle was correlated with the postoperative flexion angle (P < .01). The mean postoperative flexion angles were 110.8° ± 9.6° and 118.1° ± 8.0° in the groups with the flexion-varus angle of 6° or less and more than 6°, respectively (P = .02). Slack lateral laxity in flexion had a significant effect during knee flexion in cruciate-retaining total knee arthroplasty.