Ken Urabe

Inhibitory effects of activin-A on osteoblast differentiation during cultures of fetal rat calvarial cells.

Activin‐A is a member of the transforming growth factor‐β (TGF‐β) superfamily and is expressed by osteoblasts. However, the role of activin‐A on osteoblasts is not clearly understood. We examined the effects of activin‐A on osteoblast proliferation or differentiation, and mineralization by the osteoblasts in the first subcultures of fetal rat osteoblasts obtained from calvarial bones. Exogenous activin‐A led to impaired formation of bone nodules in a dose‐dependent manner, although it did not influence cell proliferation using an MTT assay. This inhibitory effect depended upon the time at which activin‐A was added to the culture media, and the effect was most significant when addition took place at the early phase of the culture. In addition, exogenous activin‐A inhibited gene expression of type I procollagen, alkaline phosphatase, osteonectin, and osteopontin in the cultured cells using Northern blot analysis. The peak of osteocalcin mRNA was delayed. Gene expression for TGF‐β was not influenced by exogenous activin‐A. The βA subunit (activin‐A) mRNA was detected during the early phase of this culture. These results indicate that activin‐A inhibited early differentiation of the fetal rat calvarial cells, or osteoblasts. J. Cell. Biochem. 75:206–214, 1999.

Changes in knee alignment after total knee arthroplasty.

Changes in limb alignment after total knee arthroplasty were evaluated in 20 knees replaced with the Miller Galante knee system. The mean follow-up period was 87.4 months. Seventeen of the 20 knees were in the varus position on the initial postoperative radiographs, but the alignment significantly changed to become even more aligned toward varus during the follow-up period. The thickness of the ultra-high-molecular-weight polyethylene (UHMWPE) also decreased significantly in the medial femorotibial joint. The wear of the UHMWPE possibly changed the alignment, and the postoperative alignment had a positive correlation with the wear rate. The components should be implanted so that the mechanical axis intersects the center of the components to prevent worsening of alignment as well as to minimize any such wear.

Knee stability in posterior cruciate ligament retaining total knee arthroplasty

Anteroposterior knee laxity was evaluated in 14 patients (19 knees) who had posterior cruciate ligament retaining total knee arthroplasty using the Miller Galante I prosthesis. The followup ranged from 87 to 118 months (average, 105.9 months), and the measurements were done using the KT-2000 arthrometer. The mean anteroposterior displacement with the knees with Miller Galante I prostheses was 10.1 mm at 30 degrees flexion and 8.1 mm at 75 degrees flexion. In the 15 knees with Miller Galante I prostheses with flexion greater than 90 degrees, seven had less stability at 75 degrees than at 30 degrees flexion. These knees were considered to have a nonfunctional posterior cruciate ligament, and they had a worse Knee Society score (81.1) than did the other eight knees with Miller Galante I prostheses (89.9). There were four knees in which the flexion was less than 90 degrees. In this study, approximately half of the knees with posterior cruciate ligament retaining total knee arthroplasty did not have good anteroposterior stability in flexion an average of 9 years after surgery.

Expression of parathyroid hormone‐related peptide and insulin‐like growth factor I during rat fracture healing

Parathyroid hormone‐related peptide (PTHrP) and insulin‐like growth factor I (IGF‐I) are both involved in the regulation of bone and cartilage metabolisms and their interaction has been reported in osteoblasts. To investigate the interaction of PTHrP and IGF‐I during fracture healing, the expression of mRNA for PTHrP and IGF‐I, and receptors for PTH/PTHrP and IGF were examined during rat femoral fracture healing using an in situ hybridization method and an immunohistochemistry method, respectively. During intramembranous ossification, PTHrP mRNA, IGF‐I mRNA and IGF receptors were detected in preosteoblasts, differentiated osteoblasts and osteocytes in the newly formed trabecular bone. PTH/PTHrP receptors were markedly detected in osteoblasts and osteocytes, but only barely so in preosteoblasts. During cartilaginous callus formation, PTHrP mRNA was expressed by mesenchymal cells and proliferating chondrocytes. PTH/PTHrP receptors were detected in proliferating chondrocytes and early hypertrophic chondrocytes. IGF‐I mRNA and IGF receptor were co‐expressed by mesenchymal cells, proliferating chondrocytes, and early hypertrophic chondrocytes. At the endochondral ossification front, osteoblasts were positive for PTHrP and IGF‐I mRNA as well as their receptors. These results suggest that IGF‐I is involved in cell proliferation or differentiation in mesenchymal cells, periosteal cells, osteoblasts and chondrocytes in an autocrine and/or paracrine fashion. Furthermore, PTHrP may be involved in primary callus formation presumably co‐operating with IGF‐I in osteoblasts and osteocytes, and by regulating chondrocyte differentiation in endochondral ossification.

Fibroblasts from the inner granulation tissue of the pseudocapsule in hips at revision arthroplasty induce osteoclast differentiation, as do stromal cells

Background: It has previously been shown that many osteoclast precursors are included in the granulation tissue within the pseudocapsule obtained at revision arthroplasty from hips with osteolysis. In vitro culture of only cells isolated from the granulation tissue has been previously shown to generate many mature osteoclasts. Objective: To investigate the presence or otherwise of supporting cells, similar to stromal cells, which differentiate osteoclasts within the granulation tissue. Methods: Cells isolated from the granulation tissue were cultured alone, and after four weeks fibroblast-like cells (granulation fibroblasts) remained. Rat non-adherent bone marrow cells (NA-BMCs) were co-cultured with the granulation fibroblasts with or without 1α,25(OH)2D3 (10−8 M) or heat treated ROS 17/2.8 cell conditioned medium (ht ROSCM), or both. Multinucleated cells (MNCs), which formed, were assessed by biochemical and functional characterisation of osteoclasts. Receptor activator of NFκB ligand (RANKL) was investigated by immunohistochemistry. Results: Co-culture of NA-BMCs and granulation fibroblasts caused the formation of tartrate resistant acid phosphatase (TRAP) positive MNCs, which had the calcitonin receptor (CTR), the Kat-1 antigen, which is specific to the surface of rat osteoclasts, and the ability to form pits in the presence of both 1α,25(OH)2D3 and ht ROSCM or in the presence of just ht ROSCM. RANKL was detected in fibroblast-like cells in the granulation tissue. Conclusion: These data suggest that granulation fibroblasts support osteoclast differentiation, as do osteoblasts/stromal cells, and may play a part in aseptic loosening.

New Radiographic Analysis of Sesamoid Rotation in Hallux Valgus: Comparison with Conventional Evaluation Methods

The position of the hallucal sesamoids needs to be included in evaluation of hallux valgus. In order to quantify the rotational position of the hallucal sesamoids, a new weightbearing tangential radiograph was established by means of a specially designed tangential positioning device. This device has a depression, and a tangential radiograph is taken with the metatarsophalangeal joint at 45° dorsiflexion. A lead marker plate is placed on the depression to show the horizontal plane, and the sesamoid rotation angle (SRA) is measured. The SRA is the angle between the tangential line of the most inferior aspect of the medial-lateral sesamoids and the lead marker line. The SRA was compared with values of the four-grade scale and seven-position scale which were measured from the antero-posterior view, with respect to the hallux valgus angle (HVA), by means of conventional methods. Measurements were made of 58 feet in 29 patients with hallux valgus and 64 feet in 32 normal subjects. The SRA showed the highest correlation among the three parameters (r = 0.817). Some cases had a disparity regarding the position of the sesamoids between the tangential view and the AP view due to misclassification on the AP view. We conclude that the scale of position of the sesamoid on the AP view is not valid in some cases, whereas the SRA is useful for assessing quantitatively the rotational position of the hallucal sesamoids in cases of hallux valgus.

Malposition of the tibial tubercle during flexion in knees with patellofemoral arthritis

Abstract Objective. To assess the mechanisms contributing to the induction of patellofemoral arthritis (PF-OA). Design and patients. A computed tomography scan was taken at three levels of the lower extremity in full extension and at 30° of flexion. The cuts were superimposed and 12 parameters were compared in 17 PF-OA knees and 27 normal knees to assess the rotation angle of the tibial tubercle. Results. Although the tibial tubercle was in almost the same position in full extensioin in the normal and PF-OA knees, it was positioned significantly laterally at 30° of flexion in PF-OA knees. Also the articular surface of the lateral femoral condyle was significantly narrower or steeper in PF-OA knees. Conclusion. Anatomic variations and mechanical abnormalities were identified in the PF-OA knees.

Tibial tubercle malposition in patellar joint instability: A computed tomography study in full extension and at 30° flexion

We evaluated the tibial tubercle position in knees with patellar instability. CT in full extension and at 30° flexion was used in 18 knees with instability and 18 control knees. Scans were taken at the level of the femoral epicondyles, tibial tubercle and distal tibia. We found that in full extension, the tibial tubercle was in a more lateral position in the unstable than in the control knees. At 30° flexion, the tibial tubercle in the unstable knees rotated internally, but it was never within the normal range. CT scans taken in full extension and at 30° flexion seem to be of value for ascertaining the degree of tibial tubercle malposition during knee flexion in patellar instability.

Clinical features of multiple epiphyseal dysplasia expressed in the knee

The purpose of this study is to clarify the clinical features of the knee affected by multiple epiphyseal dysplasia. Thirty-one cases of multiple epiphyseal dysplasia were reviewed. Of the patients, 11 were male and 20 were female. The average age at onset of symptoms was 22.5 years. The average age at initial visit to the authors’ hospital was 28.9 years. Radiographic findings showed epiphyseal abnormality of the knee in all but two (93%) cases. Irregularity, segmentation of the epiphysis, widening of the joint space, and genu valgum deformity were the dominant findings before epiphyseal closure. After epiphyseal closure, the most characteristic finding was a shallow femoral trochlear groove, which was observed in 56.5% of the cases. Other findings in adult patients included early onset osteoarthritic change, genu valgum, depression of the lateral tibial plateau, and multiple free bodies. However, there still is a possibility that multiple epiphyseal dysplasia exists, even if the patient lacks a shallow femoral trochlear groove. If genu valgum or varum, free bodies, and premature osteoarthritis are observed, one should evaluate other joints, keeping a diagnosis of multiple epiphyseal dysplasia in mind. Patients with knees that have a femoral trochlear groove of normal or near normal shape do exist, and premature osteoarthritic changes may develop in such patients.

A comparison of rotational landmarks in the distal femur and the tibial shaft.

The relationship among three anatomic landmarks and the mechanical axis of the tibia was evaluated using magnetic resonance imaging in 30 normal knees in 15 healthy volunteers. These three relationships are calculated for flexion and extension. The angles between the tibial mechanical axis and a line perpendicular to the surgical epicondylar axis, a line perpendicular to the clinical epicondylar axis, and the anteroposterior axis were 3.9° varus, 0.6° varus, and 0.2° valgus, respectively. The mechanical axis of the femur was 3.0° varus relative to the mechanical axis of the tibia. The results of the current study suggest that the surgical epicondylar axis rather than the clinical epicondylar axis or the anteroposterior axis can maintain a more predictable orientation with respect to the mechanical axis of the tibia when moving from flexion into extension.