Yasuhiko Takegami

R-spondin 2 facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification

Endochondral ossification is a crucial process for longitudinal growth of bones. Differentiating chondrocytes in growth cartilage form four sequential zones of proliferation, alignment into column, hypertrophy, and substitution of chondrocytes with osteoblasts. Wnt/β-catenin signaling is essential for differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage. R-spondin 2 (Rspo2), a member of R-spondin family, is an agonist for Wnt signaling, but its role in chondrocyte differentiation remains unknown. Here we report that growth cartilage of Rspo2-knockout mice shows a decreased amount of β-catenin and increased amounts collagen type II (CII) and Sox9 in the abnormally extended proliferating zone. In contrast, expression of collagen type X (CX) in the hypertrophic zone remains unchanged. Differentiating chondrogenic ATDC5 cells, mimicking proliferating chondrocytes, upregulate Rspo2 and its putative receptor, Lgr5, in parallel. Addition of recombinant human Rspo2 to differentiating ATDC5 cells decreases expressions of Col2a1, Sox9, and Acan, as well as production of proteoglycans. In contrast, lentivirus-mediated knockdown of Rspo2 has the opposite effect. The effect of Rspo2 on chondrogenic differentiation is mediated by Wnt/β-catenin signaling, and not by Wnt/PCP or Wnt/Ca(2+) signaling. We propose that Rspo2 activates Wnt/β-catenin signaling to reduce Col2a1 and Sox9 and to facilitate differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage.

Molecular hydrogen suppresses activated Wnt/β-catenin signaling

Molecular hydrogen (H2) is effective for many diseases. However, molecular bases of H2 have not been fully elucidated. Cumulative evidence indicates that H2 acts as a gaseous signal modulator. We found that H2 suppresses activated Wnt/β-catenin signaling by promoting phosphorylation and degradation οf β-catenin. Either complete inhibition of GSK3 or mutations at CK1- and GSK3-phosphorylation sites of β-catenin abolished the suppressive effect of H2. H2 did not increase GSK3-mediated phosphorylation of glycogen synthase, indicating that H2 has no direct effect on GSK3 itself. Knock-down of adenomatous polyposis coli (APC) or Axin1, which form the β-catenin degradation complex, minimized the suppressive effect of H2 on β-catenin accumulation. Accordingly, the effect of H2 requires CK1/GSK3-phosphorylation sites of β-catenin, as well as the β-catenin degradation complex comprised of CK1, GSK3, APC, and Axin1. We additionally found that H2 reduces the activation of Wnt/β-catenin signaling in human osteoarthritis chondrocytes. Oral intake of H2 water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating β-catenin accumulation. We first demonstrate that H2 suppresses abnormally activated Wnt/β-catenin signaling, which accounts for the protective roles of H2 in a fraction of diseases.

Do femoral head collapse and the contralateral condition affect patient-reported quality of life and referral pain in patients with osteonecrosis of the femoral head?

PurposesThe objectives of this study were to investigate patient-reported outcomes and referral pain at the first visit in patients with osteonecrosis of the femoral head (ONFH) and to clarify the influence of collapse of the femoral head and the contralateral condition.MethodsThe study included 105 patients (130 hips) with ONFH at the first visit, who were divided into two groups based on the presence of bilateral walking hip pain (bilateral group 25 patients, 50 hips) and unilateral hip pain (unilateral group 80 patients, 80 hips). We compared the Short Form-36 (SF-36), Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ), and visual analog scale (VAS) responses for hip, knee, and low back pain between the groups to investigate the influence of the contralateral condition. Regarding the influence of femoral head collapse, we investigated these subjects based on the stage classification in the unilateral group.ResultsThe physical component summary (PCS) of the SF-36 and all domains of the JHEQ were poorer in the bilateral group than in the unilateral group. In addition, the VAS score for low back pain was significantly poorer in the bilateral group than in the unilateral group. Regarding the collapse of the femoral head, the SF-36 for the PCS and JHEQ for pain had a significant relationship in the ONFH stage. The VAS scores for hip and knee pain had a significant relationship in the ONFH stage.ConclusionCollapse of the femoral head and the contralateral condition of ONFH strongly affect patients’ activities of daily life.

Total Hip Arthroplasty After Transtrochanteric Rotational Osteotomy for Osteonecrosis of the Femoral Head: A Mean 10-Year Follow-Up.

BACKGROUND The objective of the present study was to investigate clinical, quality of life, and radiographic outcomes of patients who underwent total hip arthroplasty (THA) after transtrochanteric rotational osteotomy (TRO) for osteonecrosis of the femoral head (ONFH). METHODS We performed a case-control study. The participants were 29 patients (34 hips) who underwent THA after TRO (TRO group). These patients had a mean age at surgery of 51.6 years (range, 30-72 years) and underwent postoperative follow-up for a mean period of 10.5 years (range, 3-19 years). For the control group (primary group), we included 58 patients (68 hips) who underwent primary THA for ONFH, matching for age and gender. RESULTS The Harris Hip Scores at the last follow-up were significantly poorer in the TRO group than in the primary group. Similarly, preoperative and postoperative hip range of motion was significantly poorer in the TRO group than in the primary group. Quality of life (Short Form-36, Oxford Hip Score, and Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire) and complication rates were not significantly different between the groups. The survival rates at 10 years, with revision for any reason as the endpoint, were 81% in the TRO group and 91% in the primary group, showing no significant difference between the groups. The TRO group had a larger average postoperative leg length discrepancy and a higher rate of stem malalignment than the primary group. CONCLUSION The clinical outcomes of THA after TRO for ONFH were poorer than those of primary THA.

The poor quality and reliability of information on periacetabular osteotomy on the internet in Japan

ABSTRACT Although many patients use the internet to access health-related information, the quality and the reliability of the information is highly inconsistent. Periacetabular osteotomy (PAO) is one of the surgical procedures for hip dysplasia. However, medical information on PAO is limited on the internet. This study aims to evaluate the quality and reliability of information available on PAO on the internet in Japan. A web search was conducted on two search engines for the following terms: “hip osteotomy,” “pelvic osteotomy,” and “osteotomy for hip preservation” in Japanese. In total, we found 120 websites. To determine the quality and reliability of information on each website, we used the Health on the Net Foundation (HON) score, the Brief DISCERN score, and an osteotomy-specific content (OSC) score. After eliminating duplicate websites, we reviewed 49 unique websites. Only three websites (6.1%) had good reliability, as indicated by their HON scores. Twelve websites (24.4%) had good-quality information, as measured by their Brief DISCERN scores. As evaluated by their OSC scores, physician websites were found to be biased toward etiology and surgical indication and did not provide information on the complications of procedures. Non-physician websites were generally insufficient. The information about PAO on the internet is, therefore, unreliable and of poor-quality for Japanese patients.

Independent association of joint space narrowing, cyst formation and health-related quality of life of patients with hip osteoarthritis in Japan

INTRODUCTION This study clarified individual associations of joint space narrowing (JSN) and radiographic features (RF) of hip osteoarthritis (HOA), i.e., cyst and osteophyte formation and subchondral sclerosis, with quality of life (QOL) in Japanese HOA patients. METHODS This cross-sectional study comprised 117 Japanese HOA patients (98 women, 17 men; mean age, 61.2 years). We recorded locations and the size of each RF and measured JSN on the acetabular side (Ace) or femoral head (FH). We evaluated pain with the Visual Analog Scale (VAS) and assessed QOL with the physical component summary (PCS) and mental component summary (MCS) of the Medical Outcomes Study Short Form-36. We compared QOL with/without the RF on the Ace, FH or both and analyzed relationships between each RF and VAS, PCS and MCS with linear regression analysis. We assessed independent associations of each RF with PCS and MCS with multiple regression analysis using various independent variables. RESULTS VAS values with the cyst on the Ace only were significantly lower than those with the cyst at both locations. PCS values with the cyst on the Ace only were significantly higher than those for both locations. Independent associations existed for maximum cyst length on the Ace and FH with VAS and for JSN with PCS, but none existed for MCS. CONCLUSIONS Our study suggested that the location and the size of the cyst formation were associated with both VAS and QOL in Japanese HOA patients. The JSN was independently associated with the PCS.

Patient-reported outcomes in patients who undergo total hip arthroplasty after periacetabular osteotomy

BACKGROUND There has been constant discussion about whether the clinical outcome of THA after periacetabular osteotomy (PAO) is equivalent to that after primary total hip arthroplasty (THA). However, there have been few reports about patient-reported outcomes (PRO) for those who undergo THA after PAO. We compared the pre- and postoperative PRO of patients who underwent THA after PAO and those who underwent primary THA alone. METHODS We performed a case-control study. Twenty-seven patients (29 hips) underwent THA after PAO (osteotomy group); their mean age at surgery was 57.2 years, and they underwent postoperative follow-up for a mean period of 3.0 years. For the control group, after matching age, sex, and Crowe classification, we included 54 patients (58 joints) who underwent primary THA for hip dysplasia. Assessment performed preoperatively and at the last follow-up included the Harris hip score, the Short Form 36 (SF-36) for the Physical Component Summary (PCS), Mental Component Summary (MCS), and Role/Social Component Summary (RCS) domains, Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ) for pain, movement, and mental health, and the visual analog scale (VAS) score of hip pain and satisfaction. RESULTS The two groups demonstrated no significant difference in the preoperative Harris hip score, each domain of the SF-36, JHEQ, and the VAS score of hip pain and satisfaction. The osteotomy group demonstrated significantly poor Harris hip scores for gait and activity, and JHEQ for movement at the last follow-up. There was no significant difference in each domain of the SF-36 and the VAS score of hip pain and satisfaction at the last follow-up. CONCLUSION Previous PAO affects the quality of physical function in patients who undergo subsequent THA.

Validity of radiographic assessment of the knee joint space using automatic image analysis

Abstract Objectives: The present study investigated whether there were differences between automatic and manual measurements of the minimum joint space width (mJSW) on knee radiographs. Methods: Knee radiographs of 324 participants in a systematic health screening were analyzed using the following three methods: manual measurement of film-based radiographs (Manual), manual measurement of digitized radiographs (Digital), and automatic measurement of digitized radiographs (Auto). The mean mJSWs on the medial and lateral sides of the knees were determined using each method, and measurement reliability was evaluated using intra-class correlation coefficients. Measurement errors were compared between normal knees and knees with radiographic osteoarthritis. Results: All three methods demonstrated good reliability, although the reliability was slightly lower with the Manual method than with the other methods. On the medial and lateral sides of the knees, the mJSWs were the largest in the Manual method and the smallest in the Auto method. The measurement errors of each method were significantly larger for normal knees than for radiographic osteoarthritis knees. Conclusions: The mJSW measurements are more accurate and reliable with the Auto method than with the Manual or Digital method, especially for normal knees. Therefore, the Auto method is ideal for the assessment of the knee joint space.

Comparison of cementless total hip arthroplasty survivorship between metal-on-highly cross-linked polyethylene and ceramic on ceramic bearings: A case control study with a 5-9-year follow-up

BACKGROUND Currently, there is a lack of evidence on the medium-term follow-up of cementless total hip arthroplasty (THA) using metal-on-highly cross-linked polyethylene bearing (MoXPE), ceramic on ceramic bearing (CoC) at more than 5 years follow-up. Therefore, we performed a case control study to: compare the incidence rate of osteolysis; compare the longevity for both types of THAs, and to evaluate the wear rate of MoXPE THAs. HYPOTHESIS CoC THAs will have a lower rate of osteolysis and better longevity than MoXPE THAs. PATIENTS AND METHODS We performed a retrospective analysis of 77 MoXPE (68 women, 9 men) and 105 CoC (85 women, 20 men) THAs, with an average patient age at the time of surgery of 64.7 years (range, 27 to 76 years). The cohorts were matched according to sex, body mass index, or diagnosis of hip joint disease. Clinical and radiologic measurements were analyzed at a mean follow-up of 6.7 years (range, 5-9 years). RESULTS There were no between-group differences with regard to the Harris hip score (87.0 [64.0-98.0] and 89.9 [70.0-100.0] for the MoXPE and CoC group, respectively) and the incidence rate of osteolysis (2.6% and 1.9%, respectively). Revision was required for 1 case for each THA type. The Kaplan-Meier survival at 8 years, using implant loosening or revision as the end-point of analysis, was 96.1% (95% confidence interval [CI], 90.0-99.3) for the MoXPE group and 98.9% (95% CI, 92.2-99.8) for the CoC group (p=0.189). The mean annual liner wear rate was 0.0160mm/year (range, 0.0050 to 0.0390mm/year) for the MoXPE THAs. DISCUSSION There was no difference between CoC and MoXPE THAs in the incidence of osteolysis or in survival rate at 8 years post-surgery. Excellent clinical and radiological outcomes were obtained for both types of bearings. LEVEL OF EVIDENCE III, Case control study, case control retrospective design.

The influence of early radiolucent lines appearing on femoral head penetration into HXLPE cemented sockets

Introduction: This study investigates differences in femoral head penetration between highly cross-linked polyethylene (HXLPE) cemented sockets both with and without radiolucent lines (RLLs) in the early postoperative phase and at 5 years follow-up. Methods: There were 35 patients (37 hips), mean age of 66.8 years, who underwent total hip arthroplasty (THA) using highly HXLPE cemented sockets. They were divided into 2 groups based on postoperative the early appearance of RLLs. Femoral head penetrations on both anteroposterior- and Lauenstein-view radiographs were evaluated, and the mean polyethylene (PE) wear rate was calculated based on femoral head penetrations between 2 and 5 years. Results: Femoral head penetrations in the proximal direction were 0.075 mm and 0.150 mm in the RLL and non-RLL groups at 1 year postoperatively (p = 0.019). At 5 years measured penetration was 0.107 mm and 0.125 mm in the RLL and non-RLL groups, respectively (p = 0.320). The mean PE wear rates in anteroposterior-view were 0.008 mm/year and 0.003 mm/year in the RLL and non-RLL groups (p = 0.390) and those in Lauenstein-view were 0.010 mm/year and 0.005 mm/year, respectively (p = 0.239). Conclusions: In the RLL group, the PE bedding-in was less compared with those in the non-RLL group. Additionally, the mean PE wear rate in the RLL group tended to be higher than that in the non-RLL group. The distribution of stress loading through the cement may differ according to whether early RLLs appear.