Tetsuya Jinno

Runx1 and Runx2 cooperate during sternal morphogenesis

Chondrocyte differentiation is strictly regulated by various transcription factors, including Runx2 and Runx3; however, the physiological role of Runx1 in chondrocyte differentiation remains unknown. To examine the role of Runx1, we generated mesenchymal-cell-specific and chondrocyte-specific Runx1-deficient mice [Prx1 Runx1f/f mice and α1(II) Runx1f/f mice, respectively] to circumvent the embryonic lethality of Runx1-deficient mice. We then mated these mice with Runx2 mutant mice to obtain mesenchymal-cell-specific or chondrocyte-specific Runx1; Runx2 double-mutant mice [Prx1 DKO mice and α1(II) DKO mice, respectively]. Prx1 Runx1f/f mice displayed a delay in sternal development and Prx1 DKO mice completely lacked a sternum. By contrast, α1(II) Runx1f/f mice and α1(II) DKO mice did not show any abnormal sternal morphogenesis or chondrocyte differentiation. Notably, Runx1, Runx2 and the Prx1-Cre transgene were co-expressed specifically in the sternum, which explains the observation that the abnormalities were limited to the sternum. Histologically, mesenchymal cells condensed normally in the prospective sternum of Prx1 DKO mice; however, commitment to the chondrocyte lineage, which follows mesenchymal condensation, was significantly impaired. In situ hybridization analyses demonstrated that the expression of α1(II) collagen (Col2a1 — Mouse Genome Informatics), Sox5 and Sox6 in the prospective sternum of Prx1 DKO mice was severely attenuated, whereas Sox9 expression was unchanged. Molecular analyses revealed that Runx1 and Runx2 induce the expression of Sox5 and Sox6, which leads to the induction of α1(II) collagen expression via the direct regulation of promoter activity. Collectively, these results show that Runx1 and Runx2 cooperatively regulate sternal morphogenesis and the commitment of mesenchymal cells to become chondrocytes through the induction of Sox5 and Sox6.

The distinct role of the Runx proteins in chondrocyte differentiation and intervertebral disc degeneration: Findings in murine models and in human disease

OBJECTIVE Runx2 is a transcription factor that regulates chondrocyte differentiation. This study was undertaken to address the role of the different Runx proteins (Runx1, Runx2, or Runx3) in chondrocyte differentiation using chondrocyte-specific Runx-transgenic mice, and to study the importance of the QA domain of Runx2, which is involved in its transcriptional activation. METHODS Runx expression was analyzed in the mouse embryo by in situ hybridization. Overexpression of Runx1, Runx2 (lacking the QA domain [DeltaQA]), or Runx3 was induced in chondrocytes in vivo, to produce alpha(1)II-Runx1, alpha(1)II-Runx2DeltaQA, and alpha(1)II-Runx3 mice, respectively, for histologic and molecular analyses. Runx expression was also examined in an experimental mouse model of mechanical stress-induced intervertebral disc (IVD) degeneration and in human patients with IVD degeneration. RESULTS Runx1 expression was transiently observed in condensations of mesenchymal cells, whereas Runx2 and Runx3 were robustly expressed in prehypertrophic chondrocytes. Similar to alpha(1)II-Runx2 mice, alpha(1)II-Runx2DeltaQA and alpha(1)II-Runx3 mice developed ectopic mineralization of cartilage, but this was less severe in the alpha(1)II-Runx2DeltaQA mice. In contrast, alpha(1)II-Runx1 mice displayed no signs of ectopic mineralization. Surprisingly, alpha(1)II-Runx1 and alpha(1)II-Runx2 mice developed scoliosis due to IVD degeneration, characterized by an accumulation of extracellular matrix and ectopic chondrocyte hypertrophy. During mouse embryogenesis, Runx2, but not Runx1 or Runx3, was expressed in the IVDs. Moreover, both in the mouse model of IVD degeneration and in human patients with IVD degeneration, there was significant up-regulation of Runx2 expression. CONCLUSION Each Runx protein has a distinct, yet overlapping, role during chondrocyte differentiation. Runx2 contributes to the pathogenesis of IVD degeneration.

Cementless total hip replacement after previous intertrochanteric valgus osteotomy for advanced osteoarthritis

We present a series of 30 uncemented total hip replacements performed between June 1985 and January 2002 with a mean follow-up of seven years (5 to 20) in 27 patients who had previously undergone a valgus intertrochanteric osteotomy. No further osteotomy was undertaken to enable hip replacement. We used a number of uncemented modular or monoblock femoral components, acetabular components and bearings. The patients were followed up clinically and radiologically. We report 100% survival of the femoral component. One acetabular component was revised at five years post-implantation for aseptic loosening. We noted cortical hypertrophy around the tip of the monoblock stems in six patients. We believe that modular femoral components should be used when undertaking total hip replacement in patients who have previously undergone valgus femoral osteotomy.

Postoperative hip motion and functional recovery after simultaneous bilateral total hip arthroplasty for bilateral osteoarthritis

BackgroundSimultaneous bilateral total hip arthroplasty (THA) can offer a potential benefit of greater postoperative hip motion without the negative influence of contralateral hip disabilities, compared to two-stage THA. However, postoperative changes in hip motion after simultaneous bilateral THA have rarely been reported. The purpose of this study was to clarify the efficacy of simultaneous procedures on postoperative hip motion and functional recovery.MethodsWe retrospectively compared hip motion in 27 patients treated with simultaneous bilateral THA to those in 11 patients with two-stage bilateral THA, 35 patients with unilateral THA for unilateral disease, and 15 patients with unilateral THA for bilateral disease. We also evaluated the clinical manifestations according to the Japanese Orthopaedic Association (JOA) hip scores and compared the outcomes among the groups. All of the THA surgeries were primarily performed through a posterolateral approach using cement-less prostheses. The diagnosis at surgery was dysplastic osteoarthritis in all patients, and the patients were followed up for at least 4 years.ResultsThe postoperative improvement of motion in hip flexion was significantly greater in patients treated with simultaneous procedures compared to patients with two-stage THA and unilateral THA for bilateral disease. The differences in improvement of motion in hip abduction were less marked than the improvement in hip flexion among the groups. Although there were no significant differences in pain scores among the groups, the values for activity of daily living were significantly greater in patients treated with simultaneous bilateral THA and patients with unilateral THA for unilateral disease than in patients with unilateral and two-stage bilateral THA for bilateral disease.ConclusionsThe simultaneous procedure was considered to be more effective in patients with bilateral hip osteoarthritis and demonstrated a substantial improvement in hip motion and functional recovery after THA.

Is closed suction drainage effective in early recovery of hip joint function? Comparative evaluation in one-stage bilateral total hip arthroplasty.

One-stage primary bilateral cementless total hip arthroplasty with unilateral closed suction drainage (CSD) was prospectively performed for 51 patients (102 hips), and local effects of CSD were quantitatively evaluated. Postoperatively, pain scores evaluated by visual analog scale and periwound temperatures measured by thermography were lower in the CSD side than the non-CSD side. CT measurements also showed that postoperative cross-sectional area of the thigh was smaller in the CSD side. Active straight leg raising and weight bearing were more accelerated in the CSD side., showing earlier recovery of hip joint function. CSD for hip arthroplasty has an advantage in reducing postoperative local inflammation and be recommended from the viewpoint of postoperative pain relief and early recovery of hip joint function.

Effect of Changing the Joint Kinematics of Knees With a Ruptured Anterior Cruciate Ligament on the Molecular Biological Responses and Spontaneous Healing in a Rat Model.

Background: The poor healing capacity of a completely ruptured anterior cruciate ligament (ACL) has been attributed to an insufficient vascular supply, cellular metabolism, and deficient premature scaffold formation because of the unique intra-articular environment. However, previous studies have focused on intra-articular factors without considering extra-articular factors, including the biomechanical aspects of ACL-deficient knees. Hypothesis: Changing the joint kinematics of an ACL-ruptured knee will improve cellular biological responses and lead to spontaneous healing through the mechanotransduction mechanism. Study Design: Controlled laboratory study. Methods: A total of 66 skeletally mature Wistar rats were randomly assigned to a sham-operated group (SO), ACL-transection group (ACL-T), controlled abnormal movement group (CAM), and an intact group (IN). The ACL was completely transected at the midportion in the ACL-T and CAM groups, and the CAM group underwent extra-articular braking to control for abnormal tibial translation. The SO group underwent skin and joint capsule incisions and tibial drilling, without ACL transection and extra-articular braking. The animals were allowed full cage activity until sacrifice at 1, 2, 4, 6, and 8 weeks postoperatively for histological, molecular biological, and biomechanical assessment. Results: All injured ACLs in the ACL-T group were not healed, but those in the CAM group healed spontaneously, showing a typical ligament healing response. Regarding the molecular biological response, there was an upregulation of anabolic factors (ie, transforming growth factor–β) and downregulation of catabolic factors (ie, matrix metalloproteinase). Examination of the mechanical properties at 8 weeks after injury showed that >50% of the strength of the intact ACL had returned. Conclusion: Our results suggest that changing the joint kinematics of knees with a ruptured ACL alters the molecular biological responses and leads to spontaneous healing. These data support our hypothesis that the mechanotransduction mechanism mediates molecular responses and determines whether the ACL will heal. Clinical Relevance: Elucidating the relationship between the mechanotransduction mechanism and healing responses in knees with completely ruptured ACLs may result in the development of novel nonsurgical treatment that enables the ACL to spontaneously heal in patients who are not suitable for reconstruction.

Is Drain Tip Culture Prognostic of Surgical Site Infection? Results of 1380 Drain Tip Cultures in Total Hip Arthroplasty

The purpose of this study was to evaluate a prognostic value of drain tip culture for surgical site infection (SSI) after total hip arthroplasty. A total of 1380 closed suction drain tips cultured after removal in primary total hip arthroplasty were included in this study. Drains were removed in 12-72 hours after surgery. Drain tip cultures were positive in 11 cases (0.8%). SSI was found in 4 cases (0.3%), where the drain tip cultures were all negative. The sensitivity of drain tip culture for infection after surgery was 0%, and the specificity was 99.7%. We concluded that, drain tip culture cannot be prognostic for SSI after total hip arthroplasty. Routine use of drain tip culture is not supported.

Comparison of different distal designs of femoral components and their effects on bone remodeling in 1-stage bilateral total hip arthroplasty.

To evaluate the effects of distal design of a proximally coated femoral component on periprosthetic bone remodeling, we prospectively performed 21 one-stage bilateral total hip arthroplasties using a distally tapered and a distally cylindrical stem with the same proximal design, randomized to side. All hips showed good outcomes clinically and radiographically at the final follow-up, average of 7 years postoperatively. Cancellous condensation was always found in Gruens zones 2 and 6 around the cylindrical stem and in regions between zones 2 and 3 and between zones 6 and 5 around the tapered stem. Bone mineral density of Gruens zones 2 and 6 was significantly lower around the tapered stem. These results suggested more distal loading in hips with the tapered stem than in those with the cylindrical stem.

Incidence of floating toe and its association with the physique and foot morphology of Japanese children

[Purpose] Physical development, foot morphology, and toe contact of children aged 3 to 5 years were assessed in order to investigate the relationships between body and foot morphology and the incidence of the condition known as “floating toe”. [Subjects] A total of 198 children, aged 3 to 5 years old, participated in this study. [Methods] Height and weight were measured for body morphology, and foot length and width were measured for foot morphology. Footprint images were taken to calculate the number of floating toes. Information about the children’s height and weight at birth, and the time of starting to walk was obtained from their guardians. [Results] At least one floating toe was observed in 87.7–98.7% of the children depending on their ages. The fifth toe was most commonly affected, occurring in 74.2% of the study population. Among the body and foot morphology parameters, only weight at birth showed a significant but very weak correlation with the number of floating toes. [Conclusion] There was a high incidence of floating toe among the children, with the fifth toe most commonly affected. Floating toe weakly but significantly correlated with weight at birth, but did not correlated with other measures of physique at birth, physical development, or the time of starting to walk.

Ranges of active joint motion for the shoulder, elbow, and wrist in healthy adults

Purpose: The aim of this study was to show highly reliable normal values and three-dimensional characteristics for final range of motion during active movements of the upper extremity joints, and to develop a database from healthy participants, with the advantage of this database lying in the methods of defining shoulder axial rotation angle and of compensating for soft tissue artifacts. Methods: We used an electromagnetic tracking system (FASTRAK) to measure three-dimensional motions of the shoulder (thoracohumeral), elbow/forearm, and wrist in 20 healthy adults (age range: 18–34 years) during active joint motion tasks of the upper extremity. Results: Joint angles of the upper extremity at the final position of joint motion tasks were determined. Highly reliable data for shoulder axial rotation angle were obtained, using a new definition of joint angle and regression analysis to compensate for estimation errors. Conclusions: These results should be useful in setting goals for the treatment of upper extremity joint functions in the fields of rehabilitation, orthopedics, and sports medicine. Implications for Rehabilitation Complex joint motions that occur naturally (unconsciously) about some axes should be taken into account in interventions for range of joint motion (ROM). The data obtained through this study simultaneously indicating multiple interrelated angles can be used as reference values for maximum active ROM. ROM in the directions of motion involved in the various tasks (for example, elevation angle during shoulder flexion) may have a role to play in evaluating and setting goals for patients with impaired ROM of the arm joints.