Koji Asaumi

Expression of connective tissue growth factor in cartilaginous tumors

Connective tissue growth factor (CTGF) predominantly is expressed in hypertrophic chondrocytes and its specific receptors are demonstrated on chondrocytic cells. Therefore, CTGF may be involved in the proliferation and/or differentiation of cartilage cells. In the current study, CTGF expression was examined both in chondrosarcoma and enchondroma to clarify the relation between the expression of CTGF and the grade of malignancy.

Expression of neurotrophins and their receptors (TRK) during fracture healing

To clarify the roles of neurotrophins and their receptors in bone formation, expression of neurotrophins and their receptors (TRK) in a model of mouse fracture healing was investigated. A total of 120 male ICR mice were studied. The right eighth rib of 70 mice was fractured. For sham operation as a control, the right eighth rib of 50 mice was similarly exposed but not fractured. Localization of TRKA, TRKB, and TRKC in a rectangular region of the rib together with surrounding soft tissues was investigated by immunostaining. Localizations of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) at the fracture callus were also investigated by immunostaining, and their mitochondrial RNA (mRNA) expressions were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR). As a result, we observed two types of neurotrophin receptors in the bone forming area: immunostaining by anti-TRKA was observed in almost all bone forming cells, and staining with anti-TRKC was observed in osteoblast-like cells and hypertrophic chondrocytes, but no staining was observed with anti-TRKB. On the other hand, localization of NGF was observed in almost all bone forming cells, localization of BDNF was observed in osteoblast-like cells, and localization of NT-3 was observed in osteoblast-like cells and hypertrophic chondrocytes at the fracture callus. Expression levels of the mRNA of three neurotrophins in the fractured rib were increased during the process of healing, especially those of NGF and NT-3, which peaked at 2 days after the fracture. The level of BDNF mRNA increased gradually over 8 days. These findings show that neurotrophins and their receptors were expressed in bone forming cells, and suggest that they are involved in the regulation of bone formation as an autocrine and paracrine factor in vivo.

Expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) during fracture healing

Localization and expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24 (CTGF/Hcs24) during fracture healing in mouse ribs were investigated. In situ hybridization demonstrated that CTGF/Hcs24 mRNA was remarkably expressed, especially in hypertrophic chondrocytes and proliferating chondrocytes, in the regions of regenerating cartilage on days 8 and 14 after fracture. CTGF/Hcs24 mRNA was also expressed in proliferating periosteal cells in the vicinity of the fracture sites on days 2 and 8, and in cells in fibrous tissue around the callus on day 8. Northern blot analysis showed that expression of CTGF/Hcs24 mRNA was 3.9 times higher on day 2 of fracture healing than that on day 0. On day 8, it reached a peak of 8.6 times higher than that on day 0. It then declined to a lower level. Immunostaining showed that CTGF/Hcs24 was localized in hypertrophic chondrocytes and proliferating chondrocytes in the regions of regenerating cartilage, and in active osteoblasts in the regions of intramembranous ossification. Although CTGF/Hcs24 was abundant in the proliferating and differentiating cells (on days 8 and 14), immunostaining decreased as the cells differentiated to form bone (on day 20). CTGF/Hcs24 was also detected in cells in fibrous tissue, vascular endothelial cells in the callus, and periosteal cells around the fracture sites. These results suggest that CTGF/Hcs24 plays some role in fracture healing.

Surgical management of hip dislocation in children with arthrogryposis multiplex congenita

Arthrogryposis multiplex congenita (AMC) is a rare disease with multiple joint contractures. It is widely believed that bilaterally dislocated hips should not be reduced since movement is satisfactory and open reduction has had poor results. Since 1977 we have performed a new method of open reduction using an extensive anterolateral approach on ten hips in five children with AMC. The mean age at surgery was 31.5 months (17 to 64) and the mean follow-up was 11.8 years (3.8 to 19.5). At the final follow-up all children walked without crutches or canes. Two managed independently, one required a long leg brace and two had short leg braces because of knee and/or foot problems. The clinical results were good in eight hips and fair in two and on the Severin classification seven hips were rated as good (group I or group II). We recommend the extensive anterolateral approach for unilateral or bilateral dislocation of the hip in children with arthrogryposis or developmental dislocation of the hip.

Expression of Connective Tissue Growth Factor/Hypertrophic Chondrocyte-Specific Gene Product 24 (CTGF/Hcs24/CCN2) During Distraction Osteogenesis

To investigate the localization and expression of connective tissue growth factor/hypertrophic chondrocyte-specific gene product 24/CCN family member 2 (CTGF/Hcs24/CCN2) during distraction osteogenesis in the rat femur, we studied a total of 54 male rats (11 weeks old). We performed osteotomy in the midshaft of the right femur. After 7 days (lag phase), distraction was started, at the rate of 0.25 mm/12 h for 21 days (distraction phase) by using a small external fixator, and this was followed by a 7-day consolidation phase. Localization and expression of CTGF/Hcs24 during distraction osteogenesis in the femur were examined by immunostaining, in situ hybridization, and reverse transcriptase polymerase chain reaction (RT-PCR). Immunostaining showed the localization of CTGF/Hcs24 in various cells located in the bone-forming area around the osteotomy site. During the distraction phase, in situ hybridization showed that CTGF/Hcs24 mRNA was expressed not only in hypertrophic chondrocytes and osteoblasts but also in fibroblast-like cells and mesenchymal cells at sites of end-ochondral ossification, and not only in osteoblasts but also in pre-osteoblasts and fibroblast-like cells at sites of intramembranous ossification. RT-PCR showed higher level expression of CTGF/Hcs24 mRNA in the distracted group than in the nondistracted group. These results revealed an elevated pattern of CTGF/Hcs24 mRNA expression during distraction osteogenesis, and suggest that CTGF/Hcs24 may play some roles in the endochondral and intramembranous ossification processes that occur during distraction osteogenesis.

The Minimally Invasive Plate Osteosynthesis (MIPO) Technique with a Locking Compression Plate for Femoral Lengthening

A minimally invasive plate osteosynthesis technique using a locking compression plate (LCP) has been used widely in trauma cases. Its advantages are that the MIPO technique does not interfere with the fracture site and thus provides improved biological healing, and that the LCP has excellent angular stability. Its use in bone lengthening, however, has not been established. In such cases, it is desirable to shorten the external skeletal fixation period as much as possible. Here, the MIPO technique using an LCP was applied to femoral distraction osteogenesis in an attempt to shorten the external skeletal fixation period. For femoral lengthening, the MIPO technique was performed in 2 stages. Orthofix external fixators (Orthofix, England) were used to insert screws from the anterolateral side rather than from the lateral side of the femur for bone lengthening. When sufficient callus formation was detected postoperatively at the site of bone lengthening, and the absence of infection was ensured, limb draping was performed, including a whole external fixator, and then the MIPO technique was applied with an LCP.In 3 cases (5 limbs), the average duration of external skeletal fixation was 134 days, the average external-fixation index was 24 days/cm, and the average consolidation index was 22 days/cm. The MIPO technique using an LCP made it possible to shorten the external skeletal fixation-wearing period in femoral lengthening.

Follow-up Study After Corrective Imhäuser Intertrochanteric Osteotomy for Slipped Capital Femoral Epiphysis

We investigated 28 hips in 26 patients with slipped capital femoral epiphysis who were treated by the Imhauser intertrochanteric osteotomy, with subsequent removal of implants. The mean age at operation was 13 years, and the mean age at the time of the final follow-up was 19 years. The physeal stability was unstable for 15 hips and stable for 13. Posterior tilting angle (PTA) ranged from 33° to 72° before operation. PTA became restored to within the allowable range of up to 30° in all patients. The limitation of range of motion completely resolved in all patients, and none had necrosis of the femoral head postoperatively. There was a mean reduction in leg length by 0.7 cm. Four patients had a fracture due to bone fragility from longterm traction and bed rest. Chondrolysis developed in only 1 male classified as an unstable case with an unstable classified as unstable. The Imhauser treatment system for mild to severe cases may be said to be reasonable in that the physeal stability is rendered stable by traction and then the PTA is reduced to 30° or less by osteotomy to lessen the severity to mild. So, satisfactory results were obtained both clinically and roentgenographically in short- or midterm outcome.

Total Knee Arthroplasty Without Patellar Resurfacing

Total knee arthroplasty (TKA) without patellar resurfacing by using cemented surface-type prosthesis (Okayama University PCL-R type) was reviewed over 1 year (average 3.3 years). They were 101 cases (137 rheumatoid and 41 osteoarthritic knees). About 15% of rheumatoid cases had mild patellofemoral (P-F) joint pain, and 24.4% of osteoarthritic (OA) cases also complained of mild pain around the patella at standing up and stair climbing, but the pain gradually reduced after 3 years in OA. In such patients with P-F joint pain, there is a tendency of lateral shifting and lateral tilting of the patella, which means incongruity of the P-F joint. Remodeling of the retropatellar surface can be seen within 2–3 years postoperatively, and such a change can reduce the P-F joint pain, especially in OA. It was concluded that P-F pain can be very slight and not hazardous for the patients daily life, if good alignment of the P-F joint is obtained during the operation.