Ryota Teshima

Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis.

Individuals with rheumatoid arthritis frequently have autoantibodies to citrullinated peptides, suggesting the involvement of the peptidylarginine deiminases citrullinating enzymes (encoded by PADI genes) in rheumatoid arthritis. Previous linkage studies have shown that a susceptibility locus for rheumatoid arthritis includes four PADI genes but did not establish which PADI gene confers susceptibility to rheumatoid arthritis. We used a case-control linkage disequilibrium study to show that PADI type 4 is a susceptibility locus for rheumatoid arthritis (P = 0.000008). PADI4 was expressed in hematological and rheumatoid arthritis synovial tissues. We also identified a haplotype of PADI4 associated with susceptibility to rheumatoid arthritis that affected stability of transcripts and was associated with levels of antibody to citrullinated peptide in sera from individuals with rheumatoid arthritis. Our results imply that the PADI4 haplotype associated with susceptibility to rheumatoid arthritis increases production of citrullinated peptides acting as autoantigens, resulting in heightened risk of developing the disease.

Correlation Between Operative Outcomes of Cervical Compression Myelopathy and Mri of the Spinal Cord

Study Design. Magnetic resonance images of cervical compression myelopathy were retrospectively analyzed in comparison with surgical outcomes. Objectives. To investigate which magnetic resonance findings in patients with cervical compression myelopathy reflect the clinical symptoms and prognosis, and to determine the radiographic and clinical factors that correlate with the prognosis. Summary of Background Data. Signal intensity changes of the spinal cord on magnetic resonance imaging in chronic cervical myelopathy are thought to be indicative of the prognosis. However, the prognostic significance of signal intensity change remains controversial. Methods. The participants in this study were 73 patients who underwent cervical expansive laminoplasty for cervical compression myelopathy. Their mean age was 64 years, and the mean postoperative follow-up period was 3.4 years. The pathologic conditions were cervical spondylotic myelopathy in 42 patients and ossification of the posterior longitudinal ligament in 31 patients. Magnetic resonance imaging (spin-echo sequence) was performed in all the patients. The transverse area of the spinal cord at the site of maximal compression was computed, and spinal cord signal intensity changes were evaluated before and after surgery. Three patterns of spinal cord signal intensity changes on T1-weighted sequences/T2-weighted sequences were detected as follows: normal/normal, normal/high-signal intensity changes, and low-signal/high-signal intensity changes. Surgical outcomes were compared among these three groups. The most useful combination of parameters for predicting prognosis was determined using a stepwise regression analysis. Results. The findings showed 2 patients with normal/normal, 67 patients with normal/high-signal, and 4 patients with low-signal/high-signal change patterns before surgery. Regarding postoperative recovery, the preoperative low-signal/high-signal group was significantly inferior to the preoperative normal/high-signal group. There was no significant difference between the transverse area of the spinal cord at the site of maximal compression in the normal/high-signal group and the low-signal/high-signal group. A stepwise regression analysis showed that the best combination of surgical outcome predictors included age (correlation coefficient R = −0.348), preoperative signal pattern, and duration of symptoms (correlation coefficient R = −0.231). Conclusions. The low-signal intensity changes on T1-weighted sequences indicated a poor prognosis. The authors speculate that high-signal intensity changes on T2 weighted images include a broad spectrum of compressive myelomalacic pathologies and reflect a broad spectrum of spinal cord recuperative potentials. Predictors of surgical outcomes are preoperative signal intensity change pattern of the spinal cord on radiologic evaluations, age at the time of surgery, and chronicity of the disease.

Structure of the most superficial layer of articular cartilage

We studied the most superficial layer of macroscopically normal articular cartilage obtained from human femoral heads, using polarising microscopy and SEM. The most superficial layer, 4 to 8 microns thick, was acellular consisting of collagen fibrils. This layer could be peeled away as a thin film, with no broken collagen fibrils on its inferior surface or on the surface of subjacent cartilage layers. The orientation and diameter of collagen fibrils were different on these two surfaces. Our findings suggest that the most superficial layer is an independent one which is only loosely connected to the fibrous structure in the layer deep to it.

Effect of parathyroid hormone on cortical bone response to in vivo external loading of the rat tibia.

Abstract Cortical bone responses following administration of parathyroid hormone (PTH) were evaluated using a four-point bending device to clarify the relationship between the effect of PTH and mechanical loading. Female Wistar rats, 36-months-old, were used. Rats were randomized into three groups (n = 10/group), namely PTH-5 (5 μg PTH/kg body weight), PTH-30 (30 μg PTH/kg body weight), and PTH-v (vehicle). PTH (human PTH (1–34)) was injected subcutaneously three times/week for 3 weeks. Loads on the right tibia were applied in vivo at 29.1 ± 0.3 N for 36 cycles at 2 Hz 3 days/week for 3 weeks using four-point bending. The administration of PTH and tibial mechanical loading were performed on the same day. After calcein double labeling, rats were killed and tibial cross-sections were prepared from the region with maximal bending at the central diaphysis. Histomorphometry was performed over the entire periosteal and endocortical surfaces of the tibiae, dividing the periosteum into lateral and medial surfaces. The in vivo average peak tibial strains (predicted) on the lateral periosteal surface were 1392.4, 1421.8 and 1384.7 μstrain in PTH-v, PTH-5 and PTH-30 groups, respectively, showing no significant difference among the three groups. Significant loading-related increases in the bone formation surface, mineral apposition rate, and bone formation rate were observed at the periosteal and endocortical surfaces. Significant differences between PTH groups were also seen. Interaction between mechanical loading and PTH was significant at both periosteal and endocortical surfaces. It is concluded that PTH has a synergistic effect on the cortical bone response to mechanical loading.

Analysis of heat shock proteins and cytokines expressed during early stages of osteoarthritis in a mouse model

OBJECTIVE Osteoarthritis (OA) is a debilitating disease of the joints. The joints of affected individuals are characterized by a progressive degeneration of articular cartilage leading to inflammation and pain. The expression of heat shock proteins (HSPs) is a ubiquitous self-protective mechanism of all cells under stress, furthermore, the synovium of osteoarthritic individuals contains high levels of cytokines. This study seeks to establish the role of HSPs and cytokines in OA. METHODS We have investigated the presence of HSPs and cytokines in articular cartilage during early stages of OA in a mouse that is known to develop spontaneous OA lesions (C57 black mouse). The articular cartilage from closely related mice (C57BL/6) was used as control. Messenger RNAs (mRNAs) for HSPs (HSP32, HSP47, HSP60, HSP70, HSP84 and HSP86) and cytokines [interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS The mRNA levels of HSP47, HSP70, HSP86, IL-6, and IFN-gamma were up-regulated in the cartilage of C57 black mice, whereas, the level of expression of HSP32, HSP60, HSP84 and IL-1 beta remained unchanged. Furthermore, the expression of IL-1 beta, IL-6, TNF-alpha and IFN-gamma mRNA was associated with expression of HSP60, HSP47, HSP70 and HSP70/HSP86 mRNA, respectively. CONCLUSIONS The findings in this study suggest that chondrocytes are conditioned under non-physiological stress during early stages of OA, In addition, among HSPs, HSP70 was associated with two different highly expressed cytokines in C57 black mice, indicating the possible role of HSP70 as a characteristic indicator of early stage of OA.

Effects of ovariectomy and estrogen replacement therapy on arthritis and bone mineral density in rats with collagen-induced arthritis

We investigated the effects of ovariectomy (ovx) and estrogen replacement therapy (ERT) on bone mineral density (BMD) and arthritis severity in rats with collagen-induced arthritis (CIA). Seven-month-old female Sprague-Dawley rats were separated into a sham group (n = 8), CIA group (n = 14), ovx group (n = 10), CIA + ovx group (n = 11), and CIA + ovx + ERT group (n = 14). In these groups, ovx was performed at 7 days, and ERT (17beta-estradiol at 20 microg/kg three times per week) was initiated 8 days after sensitization. Every 2 weeks, until 8 weeks after sensitization, arthritis score and hind paw thickness were evaluated, and BMD of the trabecular and cortical bones in the metaphysis and diaphysis of the tibia were measured by peripheral quantitative computed tomography. The arthritis score was highest in the CIA + ovx group at all timepoints after sensitization. The hind paw thickness was significantly higher in the CIA + ovx group than in the CIA group at 8 weeks after sensitization (p < 0.05). Both the arthritis score and hind paw thickness were lower in the CIA + ovx + ERT group than in the CIA + ovx group. BMD in the metaphysis was significantly decreased in both the trabecular and cortical bones in the CIA + ovx group compared with those in the CIA group at 4, 6, and 8 weeks after sensitization. In the CIA + ovx group, trabecular BMD was changed by -34 +/- 11%, and cortical BMD changed by -14 +/- 7% in the metaphysis at 8 weeks compared with those at 0 week. In the CIA group, changes of BMD in the metaphysis were -7 +/- 11% in trabecular bone and 0 +/- 7% in cortical bone. These differences of trabecular and cortical bone loss in the metaphysis were significant (both p < 0.01). BMD reduction was significantly less in the CIA + ovx + ERT group than in the CIA + ovx group at 6 and 8 weeks after sensitization. Although BMD in the diaphysis was also reduced in the groups with CIA, the degree of reduction was smaller than in the metaphysis. We conclude that ovx in CIA rats could enhance the severity of arthritis and bone loss, and that ERT could suppress arthritis and bone loss.

Clinicoradiologic study of cervical laminoplasty with posterolateral fusion or bone graft.

Study Design. A retrospective study of cervical expansive laminoplasty for cervical myelopathy from a clinicoradiologic perspective. Objective. To clarify the correlation among sagittal curvature of the cervical spine, cervical range of motion, sagittal plane translation, spinal cord atrophy, and myelopathic symptoms in patients who have undergone laminoplasty. Summary of Background Data. Laminoplasties were developed to diminish the undesirable effects of laminectomy, which include postoperative kyphotic changes and instability. However, the superiority of laminoplasty over laminectomy remains controversial. Methods. Fifty-one patients with cervical spondylotic myelopathy or ossification of the cervical posterior longitudinal ligament who underwent laminoplasty were radiologically assessed before and after surgery. The index of the sagittal curvature, intervertebral range of motion, listhesis, and the transverse area of the spinal cord at the site of maximal compression were measured to evaluate interrelations among those parameters and myelopathic symptoms. Results. There were no patients with kyphotic curvature before surgery. The postoperative curvature tended to be less lordotic. This tendency did not adversely affect postoperative symptoms. The intervertebral range of motion was significantly decreased except at C1–C2. The final C4–C5 range of motion and the postoperative myelopathic symptoms were negatively correlated. A significant correlation was observed between the postoperative spinal cord atrophy and the final myelopathic symptoms. Conclusions. The decrease in the lordotic curvature index and the decrease in the intervertebral range of motion after laminoplasty did not cause neurologic deterioration. In the C4–C5 intervertebral segment with a high incidence of listhesis, the restriction of the C4–C5 range of motion improved the clinical myelopathic symptoms. The radiologic prognostic factors were the postoperative restriction of intervertebral range of motion in preoperatively unstable segments and the anatomic reversibility of spinal cord insult.

Ultrasonographic evaluation of medial radial displacement of the medial meniscus in knee osteoarthritis

OBJECTIVE To evaluate medial radial displacement (MRD) of the medial meniscus in osteoarthritic (OA) and normal knees, with and without weight bearing, using ultrasonography (US), and to prospectively evaluate the time course of changes in MRD in OA knees. METHODS The study subjects were 78 patients with OA of the knee (69% female; mean age 66.4 years) and 20 healthy, asymptomatic subjects (70% female; mean age 64.5 years) who served as a control group. The OA stage was determined according to the Kellgren/Lawrence (K/L) radiographic grading system. US measurement of MRD was performed with subjects in the supine and standing positions. With the exception of subjects who dropped out, 58 OA knees (followup rate 74%) were evaluated at baseline and ∼1 year later. RESULTS The medial meniscus was significantly displaced radially by weight bearing in control knees (P<0.001) and in knees with K/L grades 1-3 OA (P<0.01 for each comparison). MRD in either the supine or the standing position was not significantly different between the control knees and the K/L grade 1 knees, but significant differences were noted between the control knees and K/L grade 2 or more severe OA knees (P<0.01 for each comparison). MRD of the medial meniscus had increased significantly on followup in all knees (P<0.05 for each comparison) excluding K/L grade 4 knees in the standing position. CONCLUSION MRD of the medial meniscus increased with weight bearing and during followup. These findings suggest a close association between extraarticular displacement of the medial meniscus and progression of OA.

Insufficiency fracture of the femoral head in patients with severe osteoporosis-report of 2 cases

(1999). Insufficiency fracture of the femoral head in patients with severe osteoporosis-report of 2 cases. Acta Orthopaedica Scandinavica: Vol. 70, No. 1, pp. 87-89.

Development of the attachment zones in the rat anterior cruciate ligament: changes in the distributions of proliferating cells and fibrillar collagens during postnatal growth.

The development of the attachment zones of the anterior cruciate ligament (ACL) is an important consideration when examining the structural properties. The aim of this study was to elucidate the morphological changes and the distribution of proliferating cells and collagen types I, II and III at the attachment zones of the rat ACL during postnatal growth.