Yutaka Yabe

Joint Immobilization Induced Hypoxic and Inflammatory Conditions in Rat Knee Joints

The purpose of this study was to examine the hypoxic and inflammatory conditions after immobilization in the joint capsule of rat knees. The unilateral knee joints of adult male rats were immobilized with an internal fixator (Im group) for 1 day, 3 days, and 1, 2, 4, 8, and 16 weeks. Sham-operated animals had holes drilled in the femur and tibia and screws inserted without a plate (control group). The number of cells and blood vessels in the capsule were histologically examined. The hypoxic condition in the capsule was histologically examined with a Hypoxyprobe™-1. The gene expressions related to the hypoxic (hypoxia inducible factor-1α, vascular endothelial growth factor, and fibroblast growth factor 2) and inflammatory conditions [interleukin-6 (IL-6), IL-1α, IL-1β, tumor necrosis factor-α, and tumor necrosis factor-β] were evaluated by quantitative reverse transcription polymerase chain reaction. The number of cells was unchanged at 1 day in the two groups; however, the number significantly increased at 3 days in the Im group. The number of blood vessels in the Im group gradually decreased. Strong immunostaining of Hypoxyprobe™-1 around the blood vessels was observed in the Im group. The gene expressions of hypoxia inducible factor-1α and fibroblast growth factor 2 were significantly higher in the Im group compared with those in the control group. The gene expressions of IL-6, IL-1α, IL-1β, and tumor necrosis factor-β were significantly higher in the Im group compared with those in the control group. These data indicated that joint immobilization induced hypoxic and inflammatory conditions in the joint capsule, which might be an initiating factor for joint contracture.

Chondrogenic and fibrotic process in the ligamentum flavum of patients with lumbar spinal canal stenosis.

Study Design. A histological, biological, and immunohisto-chemical study of human lumbar ligamentum flavum. Objective. To analyze changes in the hypertrophied ligamentum flavum and clarify their etiology. Summary of Background Data. Hypertrophy of the ligamentum flavum has been considered a major contributor to the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported some factors related to ligamentum flavum hypertrophy, its etiology is still unclear. Methods. Ligamentum flavum samples were collected from 20 patients with LSCS (LSCS group) and 10 patients with lumbar disc herniation (LDH group) as a control. The thickness of the ligamentum flavum was measured histologically. The amounts of elastic fibers and proteoglycans were assessed by Elastica-Masson staining and alcian blue staining, respectively. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative reverse transcription–polymerase chain reaction and immunohistochemistry. The total genes of the 2 groups were compared by DNA microarray analysis. Results. The ligamentum flavum was significantly thicker in the LSCS group, which had a smaller amount of elastic fibers and a larger amount of proteoglycans. The gene expression related to fibrosis was significantly higher in the LSCS group; however, the immunoreactivities of collagen types I and III were weaker on the dorsal side of the ligamentum flavum in the LSCS group. The gene expression related to chondrogenesis and proteoglycan synthesis was significantly higher in the LSCS group. There was no significant difference in the gene expression related to inflammation between the 2 groups. Conclusion. Synthesis of the collagenous fibers and degradation of the elastic and collagenous fibers are both accelerated in the ligamentum flavum of patient with LSCS, which may be the reason for hypertrophy of the tissue. In addition, chondrogenesis and proteoglycan synthesis may have critical roles in the pathogenesis of the ligamentum flavum hypertrophy. Level of Evidence: 5

Joint haemorrhage partly accelerated immobilization-induced synovial adhesions and capsular shortening in rats

AbstractPurpose To elucidate the effects of intra-articular haemorrhage on the joint capsule of immobilized knees in rats.Methods The unilateral knee joints were immobilized using a plastic plate and screws. Sham operated rats had only screws inserted. A single injection of fresh autologous blood was given postoperatively into the knee joints of the immobilized blood injection (Im-B) and the Sham blood injection (Sm-B) groups. Normal saline was administered for the immobilized-saline injection (Im-S) group. Sagittal sections were prepared from the medial midcondylar region of the knee and assessed with histological, histomorphometric, and immunohistochemical methods. The range of motion (ROM) was measured, and the mechanical property of the capsule was assessed by scanning acoustic microscope.ResultsAbsorption of the injected blood was delayed and made severe adhesions in the Im-B group. The length of the synovial membrane in the Im-B group was significantly shorter than that of the other groups. The ROM was significantly restricted in the Im-B group compared with the other groups. The elasticity of the posterior capsule in the Im-B group was significantly lower than that in the Sm-B group. Iron deposition was observed in the Im-B and Sm-B groups. Strong immunoreactivities of CD68, TGF-β1, and α-SMA were observed in the adhesion area of the Im-B group. Joint immobilization with blood injection caused severe capsular adhesion and limited range of motion. Immunostaining related to fibrosis increased with joint haemorrhage.ConclusionIntra-articular haemorrhage with joint immobilization might be an accelerated risk factor for joint contracture. It is likely that leaving a haematoma inside an immobilized joint should be avoided.

Association Between Sleep Disturbance and New-onset Subjective Shoulder Pain in Survivors of the Great East Japan Earthquake: A Prospective Cohort Study in Miyagi Prefecture

The Great East Japan Earthquake (GEJE) and Tsunami devastated the northeastern coast of Japan on March 11, 2011. This study attempted to determine whether socio-psychological factors such as sleep disturbance and psychological distress influenced new-onset subjective shoulder pain in survivors, during the post disaster phase of the GEJE. From November 2012 to February 2013 (2 years after the GEJE) and November 2014 to January 2015 (4 years after the GEJE), survivors (18 years old or over) answered self-reported questionnaires. In total, 1,454 survivors responded to the questionnaires and were thus included in this study. New-onset subjective shoulder pain was defined as shoulder pain by encircled response absent at 2 years, and present at 4 years after the GEJE. Two years after the GEJE, ≥ 10/24 points on the Kessler Psychological Distress Scale-6, and ≥ 6/24 points on the Athens Insomnia Scale defined the presence of psychological distress and sleep disturbance, respectively. Multiple logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of the association between new-onset subjective shoulder pain, and psychological distress or sleep disturbance. Amongst participants, 7.2% (105/1,454) reported new-onset subjective shoulder pain. Sleep disturbance was significantly associated with new-onset subjective shoulder pain (OR = 1.92, 95% CI = 1.24-2.98, P = 0.004); however, psychological distress was not (OR = 0.78, 95% CI = 0.42-1.42, P = 0.41). In conclusion, this is the first study indicating an association between sleep disturbance and new-onset subjective shoulder pain amongst the survivors of the GEJE.

Thoracic radiculopathy caused by ossification of the ligamentum flavum.

Abstract Thoracic ossification of the ligamentum flavum (OLF) has been widely recognized as a main cause of thoracic myelopathy in Asia, particularly in Japan. However, thoracic OLF rarely causes radiculopathy. We report a rare case of thoracic radiculopathy caused by OLF. A 67-year-old male presented with a chief complaint of back pain radiating to the right of the abdomen. Neurological examination revealed mild sensory deficit at the right side of the abdomen at the T9–10 level. Magnetic resonance imaging and computed tomography demonstrated OLF at the right T9–10 level. Thoracic radiculopathy caused by OLF was suspected. Because conservative treatment was not effective to this lesion, surgical intervention was performed, and the pain disappeared immediately after the operation. Thoracic OLF rarely causes radiculopathy, but it should be considered as a differential diagnosis of thoracic radicular pain. When conservative treatment is not effective in this lesion, surgical treatment should be considered.

Heterotopic Ossification of the Distal Portion of Biceps Femoris

Heterotopic ossification is the formation of mature lamellar bone in soft tissue. We report a very unusual case of heterotopic ossification arising in the distal portion of the biceps femoris muscle. A 29-year-old woman presented with knee pain after playing golf. She had had no apparent history of trauma. Radiography of the knee showed a calcified mass adjacent to the lateral side of her knee joint. The radiological diagnosis was calcification of the lateral collateral ligament. The pain soon disappeared without treatment. At the age of 45 years, she complained of a growing mass in her left knee that was occasionally painful. Computed tomography and magnetic resonance imaging demonstrated a well matured ossified mass in the lateral side of her left knee. Radiologically and macroscopically, it was found to be in continuity with the distal part of biceps femoris. The mass was excised en bloc. Microscopically, the lesion was mainly composed of well-matured lamellar bone with bone marrow and islands of cartilage showing enchondral ossification. No apparent zoning was found. Cellular atypia was not observed. Extraskeletal osteosarcoma was ruled out. The mass was diagnosed as a heterotopic ossification arising from the distal part of biceps femoris.

Osteolipoma arising adjacent to the sternoclavicular joint. A case report.

A 45-year-old woman presented with one-year history of a mass on her chest. Computed tomography and magnetic resonance imaging demonstrated a tumour near the sternoclavicular joint. The tumour was diagnosed as osteolipoma histologically after resection. Osteolipoma is a rare tumour and this may be the first report of osteolipoma arising adjacent to the sternoclavicular joint.

Quantitative in vivo biocompatibility of new ultralow-nickel cobalt-chromium-molybdenum alloys.

Nickel (Ni) eluted from metallic biomaterials is widely accepted as a major cause of allergies and inflammation. To improve the safety of cobalt–chromium–molybdenum (Co–Cr–Mo) alloy implants, new ultralow‐Ni Co–Cr–Mo alloys with and without zirconium (Zr) have been developed, with Ni contents of less than 0.01%. In the present study, we investigated the biocompatibility of these new alloys in vivo by subcutaneously implanting pure Ni, conventional Co–Cr–Mo, ultralow‐Ni Co–Cr–Mo, and ultralow‐Ni Co–Cr–Mo with Zr wires into the dorsal sides of mice. After 3 and 7 days, tissues around the wire were excised, and inflammation; the expression of IL‐1β, IL‐6, and TNF‐α; and Ni, Co, Cr, and Mo ion release were analyzed using histological analyses, qRT‐PCR, and inductively coupled plasma mass spectrometry (ICP‐MS), respectively. Significantly larger amounts of Ni eluted from pure Ni wires than from the other wires, and the degree of inflammation depended on the amount of eluted Ni. Although no significant differences in inflammatory reactions were identified among new alloys and conventional Co–Cr–Mo alloys in histological and qRT‐PCR analyses, ICP‐MS analysis revealed that Ni ion elution from ultralow‐Ni Co–Cr–Mo alloys with and without Zr was significantly lower than from conventional Co–Cr–Mo alloys. Our study, suggests that the present ultralow‐Ni Co–Cr–Mo alloys with and without Zr have greater safety and utility than conventional Co–Cr–Mo alloys.

Decreased elastic fibers and increased proteoglycans in the ligamentum flavum of patients with lumbar spinal canal stenosis.

Elastic fibers and proteoglycans are major components of the extracellular matrix and their changes have been reported in some pathological conditions. Further, recent studies have indicated that some glycosaminoglycans and proteoglycans inhibit elastic fiber assembly. The purpose of this study was to investigate changes of the elastic fibers and proteoglycans in the ligamentum flavum and analyze their relationships to thickening of the ligamentum flavum from lumbar spinal canal stenosis (LSCS). Ligamentum flavum samples were collected from 20 patients with LSCS (thickened flavum group) and 10 patients with lumbar disc herniation (non‐thickened flavum group) as a control. Elastica–Masson staining and alcian blue staining were used to compare the relationship between the changes in the elastic fibers and proteoglycans. Gene and protein expressions of the elastic fibers and proteoglycans were analyzed by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. Histological changes indicated that proteoglycans mainly increased on the dorsal side of the ligamentum flavum in accordance with the decreased elastic fibers in the thickened flavum group. The gene and protein expressions of fibrillin‐2 and DANCE were significantly lower and decorin, lumican, osteoglycin, and versican were significantly higher in the thickened flavum group. Our study shows that elastic fibers decrease and proteoglycans increase in the thickened ligamentum flavum. Decreased gene expression of elastogenesis and disrupted elastic fiber assembly caused by increased proteoglycans may lead to a loss of elasticity in the thickened ligamentum flavum. Decreased elasticity may cause buckling of the tissue, which leads to thickening of the ligamentum flavum.

Ultrasonic and photoacoustic imaging of knee joints in normal and osteoarthritis rats

Osteoarthritis (OA) is a common joint disorder and estimated to cause symptoms in 20-40% of the elderly population. 532 nm laser is much absorbed in developed vascular network in the spongy bone which is one of the main characteristics of OA. In this study, a photoacoustic (PA) imaging system with 532 nm laser and 50 MHz US (ultrasound) transducer was developed. Normal and OA knee joints were observed by US and PA imaging. PA signal from the spongy bone was strong where US reflection was very weak. PA signal from the spongy bone was significantly strong in OA compared with that in normal knee while US showed similar low intensity echo in normal and OA. Detailed structure and information on vascular density of spongy bone in rat knee joint were successfully obtained with US / PA combined imaging. US / PA imaging should be useful for early diagnosis of OA.