Akinobu Nishimura

Functional Recovery of the Donor Knee After Autologous Osteochondral Transplantation for Capitellar Osteochondritis Dissecans

Background: Osteochondral autograft transplantation has been advocated to treat severe osteochondritis dissecans of the humeral capitellum in throwing athletes to reproduce the normal hyaline cartilage and achieve long-term elbow function. Although some authors have reported good outcomes, the current authors are concerned about functional recovery of the donor knee after osteochondral grafts have been harvested. Purpose: The present prospective study analyzed functional recovery of the donor knee after osteochondral graft harvest. Study Design: Case series; Level of evidence, 4. Methods: Twelve male patients (average age at surgery, 14.4 years) had severe osteochondritis dissecans of the humeral capitellum treated with osteochondral autograft transplantation from the contralateral knee joint. The donor knee of each patient was assessed for pain (visual analog scale), joint effusion, Lysholm score, radiographic findings, and muscle strength (60 and 180 deg/sec). Results: At 3 months after surgery, 10 patients were pain-free (visual analog scale score, 0); none had knee joint effusion; and 10 gained 100 points in the Lysholm score. However, muscle power (60 deg/sec) of the knee extensor revealed 8 patients with reduced muscle strength at 3 months compared with the preoperative level, although 11 patients reached preoperative knee extensor muscle strength at 12 months. Radiographic findings at 24 months showed that none of the patients had knee osteoarthritis. Conclusion: A time lag was evident in recovery between postoperative symptoms and muscle power at 3 months. However, harvesting osteochondral grafts did not exert adverse effects on donor knee function in young athletes at 2 years after undergoing osteochondral autograft transplantation for capitellar osteochondritis dissecans.

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma.

Nuclear factor-kappa B (NF-κB) has a pivotal role in the progression and distant metastasis of cancers, including malignant bone tumors. To inhibit NF-κB activation, a new molecular therapy using synthetic double-stranded oligodeoxynucleotide (ODN) as a ‘decoy’ cis element against NF-κB has been developed. To determine whether pulmonary metastasis of osteosarcoma is reduced by inhibiting the action of NF-κB, NF-κB decoy ODN was transfected into the nuclei of murine osteosarcoma cells with high pulmonary metastatic potential, the LM8 cell line, using a three-dimensional alginate spheroid culture model. An in vitro study demonstrated the successful transfection of LM8 cells cultured in alginate beads by ‘naked’ NF-κB decoy ODN and that the activation of NF-κB signaling was significantly suppressed. Tumor growth was not affected by transfection of NF-κB decoy ODN, however, the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) mRNA was markedly decreased. Furthermore, the transfection of ‘naked’ NF-κB decoy ODN effectively suppressed pulmonary metastasis in an in vivo alginate bead transplantation model. Our results suggest that NF-κB has a central and specific role in the regulation of tumor metastasis and could be a molecular target for development of anti-metastatic treatments for osteosarcoma.

Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis

Dual-specificity phosphatase 2 (Dusp2; also called phosphatase of activated cells 1, PAC1) is highly expressed in activated immune cells. We examined whether a potential inhibitor of Dusp2, salubrinal, prevents inflammatory cytokine expression in immune cells and arthritic responses in a mouse model of anti-collagen antibody-induced arthritis (CAIA). Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). In this study, we examined the effects of salubrinal on expression of inflammation linked genes as well as a family of DUSP genes using genome-wide microarrays, qPCR, and RNA interference. We also evaluated the effects of salubrinal on arthritic responses in CAIA mice using clinical and histological scores. The results revealed that salubrinal decreased inflammatory gene expression in macrophages, T lymphocytes, and mast cells. Dusp2 was suppressed by salubrinal in LPS-activated macrophages as well as PMA/ionomycin-activated T lymphocytes and mast cells. Furthermore, a partial silencing of Dusp2 downregulated IL1β and Cox2, and the inflammatory signs of CAIA mice were significantly suppressed by salubrinal. Collectively, this study presents a novel therapeutic possibility of salubrinal for inflammatory arthritis such as RA through inhibition of Dusp2.

Osteoporosis, vertebral fractures and mortality in a Japanese rural community

Abstract Objectives. The present study aims to determine the relationship between osteoporosis (OP), vertebral fracture (VF) and mortality. Methods. We followed up 1024 residents of Miyagawa village every 2 years for a mean of 8.4 years between 1997 and 2009. The residents were assessed every 2 years. We defined OP as T scores for bone mineral density that were < 2.5 standard deviations below peak bone mass. VF was assessed by lateral radiography of the thoracic and lumbar spine. The participants were allocated as follows depending on the presence or absence of OP and VF: with OP and without VF (OP group), with VF and without OP (VF group), with OP and VF (OP + VF group) and without OP and VF (Control group). We determined survival/mortality rates until 2011 by reviewing medical histories and death certificates. Results. By 2011, 304 participants had died. The respective 5-year survival rates for the OP + VF, OP, VF and Control groups were 80.6%, 93.7%, 87.8% and 94.2%. Mortality rates were significantly worse for the OP + VF group than the Control group (OP + VF Hazard Ratio: 1.89; 95% CI, 1.27–2.77). Conclusion. Prevention of osteoporotic VF in elderly persons is very important from the viewpoint of increasing life expectancy.

The adverse effect of an unplanned surgical excision of foot soft tissue sarcoma

BackgroundMalignant soft tissue tumors of the foot are extremely rare and thus can be prematurely excised without appropriate preoperative evaluation. The present study compares adverse effects between unplanned and planned surgical excisions.MethodsWe retrospectively reviewed the clinical records, radiographs, pathology reports and pathological specimens of 14 consecutive patients with soft tissue sarcoma of the foot among 592 with sarcomas between 1973 and 2009. We then compared the incidence and clinical outcomes after unplanned (UT; n = 5) and planned (PT; n = 9) surgical excisions of foot sarcomas.ResultsThe most frequent diagnosis was synovial sarcoma (n = 4; 28.6%). The overall 5-year survival rates of the PT and UT groups were 65.6% and 60.0%, respectively, and the event-free 5-year survival rates were 63.5% and 40.0%, respectively. Event-free and overall survival rates did not significantly differ between the two groups. However, tumors were significantly larger in the PT group than in the UT group (p < 0.05).ConclusionsUnplanned resection lead to a relatively worse prognosis and a likelihood of recurrence despite additional resections. We recommend that soft tumors of the foot should only be excised after appropriate preoperative evaluation regardless of the size of the tumor.

Influence of green tea catechins on oxidative stress metabolites at rest and during exercise in healthy humans

OBJECTIVES The aim of this study was to investigate the effects of green tea catechins (GTC) on oxidative stress metabolites in healthy individuals while at rest and during exercise. The effects investigated included response to fat metabolism, blood lactate concentrations, and rating of perceived exertion. METHODS In a paralleled, crossover, randomized controlled study, 16 trained male gymnastic students were randomly divided into two groups. The rest group (n = 8; GTC-NEX) received a single dose of 780 mg GTC with water but no exercise; the exercise group (n = 8; GTC-EX) received a similar dose of GTC but were instructed to exercise. This was followed by a crossover study with similar exercise regime as a placebo group (PL-EX) that received water only. Blood samples were collected at baseline and after 60 and 120 min of GTC intake. Oxidative stress blood biomarkers using the diacron reactive oxygen metabolite (d-ROMs) and biological antioxidant potential (BAP) tests; urinary 8-hydroxydeoxyguanosine (8-OHdG); 8-OHdG/creatinine; and blood lactate concentrations were analyzed. During the cycle ergometer exercise, volume of maximal oxygen uptake, volume of oxygen consumption, volume of carbon dioxide, and respiratory exchange ratio were measured from a sample of respiratory breath gas collected during low, moderate, and high intensity exercising, and the amount of fat burning and sugar consumption were calculated. Analysis of variance was used to determine statistical significance (P < 0.05) between and among the groups. RESULTS Levels of postexercise oxidative stress metabolites BAP and d-ROMs were found significant (P < 0.0001) in the PL-EX and GTC-EX groups, and returned to pre-exercise levels after the recovery period. Levels of d-ROMs showed no significant difference from baseline upon GTC intake followed by resting and a resting recovery period in the GTC-NEX group. BAP levels were significant upon GTC intake followed by resting (P = 0.04), and after a resting recovery period (P = 0.0006) in the GTC-NEX group. Urinary 8-OHdG levels were significant (P < 0.005) for all groups after the recovery period. A significant difference was noticed between the ratios of resting BAP to d-ROMs and exercise-induced BAP to d-ROMs (P = 0.022) after 60 min of GTC intake, as well as resting 8-OHdG and exercise-induced 8-OHdG levels (P = 0.004) after the recovery period. Oxidative potentials were higher when exercise was performed at low to moderate intensity, accompanied by lower blood lactate concentration and higher amounts of fat oxidation. CONCLUSIONS The results of the present study indicate that single-dose consumption of GTC influences oxidative stress biomarkers when compared between the GTC-NEX and GTC-EX groups, which could be beneficial for oxidative metabolism at rest and during exercise, possibly through the catechol-O-methyltransferase mechanism that is most often cited in previous studies.

Recurrent knee valgus deformity in Ellis-van Creveld syndrome.

We report a case of recurrent knee valgus deformity in a patient with Ellis-van Creveld syndrome. Varus osteotomy, distraction osteogenesis, or epiphyseal stapling is one treatment option for valgus malalignment to improve appearance, gait, and function. However, surgical correction of valgus knee deformity by varus osteotomies of the proximal tibia was not maintained postoperatively, necessitating additional varus osteotomies of the distal femur in this case. The main cause of recurrence was attributed to large bony defect of the anterior segment of the proximal tibia, in addition to depression of the lateral tibial plateau.

Predicting and validating the pathway of Wnt3a-driven suppression of osteoclastogenesis

Wnt signaling plays a major role in bone homeostasis and mechanotransduction, but its role and regulatory mechanism in osteoclast development are not fully understood. Through genome-wide in silico analysis, we examined Wnt3a-driven regulation of osteoclast development. Mouse bone marrow-derived cells were incubated with RANKL in the presence and absence of Wnt3a. Using microarray mRNA expression data, we conducted principal component analysis and predicted transcription factor binding sites (TFBSs) that were potentially involved in the responses to RANKL and Wnt3a. The principal component analysis predicted potential Wnt3a responsive regulators that would reverse osteoclast development, and a TFBS prediction algorithm indicated that the AP1 binding site would be linked to Wnt3a-driven suppression. Since c-Fos was upregulated by RANKL and downregulated by Wnt3a in a dose-dependent manner, we examined its role using RNA interference. The partial silencing of c-Fos suppressed RANKL-driven osteoclastogenesis by downregulating NFATc1, a master transcription factor of osteoclast development. Although the involvement of c-Myc was predicted and partially silencing c-Myc slightly reduced the level of TRAP, c-Myc silencing did not alter the expression of NFATc1. Collectively, the presented systems-biology approach demonstrates that Wnt3a attenuates RANKL-driven osteoclastogenesis by blocking c-Fos expression and suggests that mechanotransduction of bone alters the development of not only osteoblasts but also osteoclasts through Wnt signaling.

Vascular safety during arthroscopic all-inside meniscus suture

AbstractPurpose The purpose of the study is to assess the orientation and distance of the popliteal artery (PA) from both the anteromedial and anterolateral portals. MethodsThe records of 97 patients (100 knees) who underwent knee arthroscopy were reviewed. The shortest distance from the posterior tibial cortex to the PA on the lines from both the medial and lateral borders of the patellar tendon to the PA was evaluated by magnetic resonance imaging at full knee extension. The figure-of-four position was compared between patients with intact and deficient anterior cruciate ligaments (ACLs). The shortest distances from the posterior cruciate ligament (PCL) to the lines running from the medial and lateral borders of the patellar tendon to the PA were also measured.ResultsThe shortest distances from the posterior tibial cortex to the PA were significantly longer in the figure-of-four position than at full knee extension and during extension in the ACL-deficient than intact group. Distances did not significantly differ in the figure-of-four position. The PA was hidden from the anteromedial portal by the PCL, but remained vulnerable from the anterolateral portal.ConclusionsAll-inside meniscus suturing of the posterior horn of the lateral meniscus inserted through the anteromedial portal is safer when the knee is in the figure-of-four position than fully extended. Meniscus repairs should be completed before ACL reconstruction due to vascular positions and the ease of approach.Level of evidenceProspective correlation study, Level IV.

Arthroscopically assisted minimally invasive plate osteosynthesis for posterior fracture–dislocation of the shoulder

Proximal humeral fractures are becoming increasingly common, and treatment of displaced proximal humeral fractures remains a challenge. Minimally invasive plate osteosynthesis (MIPO), which provides early functional recovery, is a promising treatment option for proximal humeral fractures [1]. We report a patient with posterior fracture–dislocation of the shoulder who was successfully treated with arthroscopic reduction and plate fixation via a minimally invasive approach.