The lower Osteotomy Level is Associated With Decreased Revision Surgery Due to Mechanical Complications After Three-Column Osteotomy in Patients With Adult Spinal Deformity: A Multi-Institutional Retrospective Study.

STUDY DESIGN: A multi-institutional retrospective study. OBJECTIVES: To investigate risk factors of mechanical failure in three-column osteotomy (3COs) in patients with adult spinal deformity (ASD), focusing on the osteotomy level. METHODS: We retrospectively reviewed 111 patients with ASD who underwent 3COs with at least 2 years of follow-up. Radiographic parameters, clinical data on early and late postoperative complications were collected. Surgical outcomes were compared between the low-level osteotomy group and the high-level osteotomy group: osteotomy level of L3 or lower group (LO group, n = 60) and osteotomy of L2 or higher group (HO group, n = 51). RESULTS: Of the 111 patients, 25 needed revision surgery for mechanical complication (mechanical failure). A lower t-score (odds ratio [OR] .39 P = .002) and being in the HO group (OR 4.54, P = .03) were independently associated with mechanical failure. In the analysis divided by the osteotomy level (LO and HO), no difference in early complications or neurological complications was found between the two groups. The rates of overall mechanical complications, rod failure, and mechanical failure were significantly higher in the HO group than in the LO group. After propensity score matching, mechanical complications and failures were still significantly more observed in the HO group than in the LO group (P = .01 and .029, respectively). CONCLUSIONS: A lower t-score and osteotomy of L2 or higher were associated with increased risks of mechanical failure. Lower osteotomy was associated with better correction of sagittal balance and a lower rate of mechanical complications.

K-Line Tilt is a Predictor of Postoperative Kyphotic Deformity After Laminoplasty for Cervical Myelopathy Caused by Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: Retrospective single-center study. OBJECTIVES: K-line is a decision-making tool to determine the appropriate surgical procedures for patients with cervical ossification of the posterior longitudinal ligament (C-OPLL). Laminoplasty (LAMP) is one of the standard surgical procedures indicated on the basis of K-line measurements (+: OPLL does not cross the K-line). We investigated the impact of K-line tilt, a radiographic parameter of cervical sagittal balance measured using the K-line, on surgical outcomes after LAMP. METHODS: The study included 62 consecutive patients with K-line (+) C-OPLL who underwent LAMP. The following preoperative and postoperative radiographic measurements were evaluated: (1) the K-line, (2) K-line tilt (an angle between the K-line and vertical line), (3) center of gravity of the head -C7 sagittal vertical axis, (4) C2-C7 lordotic angle, (5) C7 slope, and (6) C2-C7 range of motion. Clinical results were evaluated using the Japanese Orthopedic Association scoring system for cervical myelopathy (C-JOA score). RESULTS: All the patients had non-kyphotic cervical alignment (CL ≥ 0°) preoperatively; however, kyphotic deformity (CL < 0°) was observed in 6 patients (9.7%) postoperatively. The recovery rate of the C-JOA scores was poor in the kyphotic deformity (+) group (7.8%) than in the kyphotic deformity (-) group (47.5%). The K-line tilt was identified to be a preoperative risk factor in the multivariate analysis, and the cutoff K-line tilt for predicting the postoperative kyphotic deformity was 20°. CONCLUSIONS: LAMP is not suitable for K-line (+) C-OPLL patients with K-line tilts >20°.

Detecting ossification of the posterior longitudinal ligament on plain radiographs using a deep convolutional neural network: a pilot study.

BACKGROUND CONTEXT: Its rare prevalence and subtle radiological changes often lead to difficulties in diagnosing cervical ossification of the posterior longitudinal ligament (OPLL) on plain radiographs. However, OPLL progression may lead to trauma-induced spinal cord injury, resulting in severe paralysis. To address the difficulties in diagnosis, a deep learning approach using a convolutional neural network (CNN) was applied. PURPOSE: The aim of our research was to evaluate the performance of a CNN model for diagnosing cervical OPLL. STUDY DESIGN AND SETTING: Diagnostic image study. PATIENT SAMPLE: This study included 50 patients with cervical OPLL, and 50 control patients with plain radiographs. OUTCOME MEASURES: For the CNN model performance evaluation, we calculated the area under the receiver operating characteristic curve (AUC). We also compared the sensitivity, specificity, and accuracy of the diagnosis by the CNN with those of general orthopedic surgeons and spine specialists. METHODS: Computed tomography was used as the gold standard for diagnosis. Radiographs of the cervical spine in neutral, flexion, and extension positions were used for training and validation of the CNN model. We used the deep learning PyTorch framework to construct the CNN architecture. RESULTS: The accuracy of the CNN model was 90% (18/20), with a sensitivity and specificity of 80% and 100%, respectively. In contrast, the mean accuracy of orthopedic surgeons was 70%, with a sensitivity and specificity of 73% (SD: 0.12) and 67% (SD: 0.17), respectively. The mean accuracy of the spine surgeons was 75%, with a sensitivity and specificity of 80% (SD: 0.08) and 70% (SD: 0.08), respectively. The AUC of the CNN model based on the radiographs was 0.924. CONCLUSIONS: The CNN model had successful diagnostic accuracy and sufficient specificity in the diagnosis of OPLL.

A comparative study of surgical outcomes between anterior cervical discectomy with fusion and selective laminoplasty for cervical spondylotic myelopathy.

BACKGROUND: Few studies have directly compared anterior and posterior surgical approaches in cervical spondylotic myelopathy (CSM) patients with short-segment disease. We aimed to examine and compare surgical outcomes of anterior cervical discectomy with fusion (ACDF) and selective laminoplasty (S-LAMP) in CSM patients with 1- or 2-level disease. METHODS: Forty-six patients, who received surgeries for CSM, were prospectively investigated; 24 underwent ACDF and 22 underwent S-LAMP. Average follow-up was 3.5 years. The following pre- and postoperative radiographic measurements were recorded: (1) C2-7 angle, (2) local angle (lordotic Cobb angle at operative level), (3) cervical sagittal vertical axis (SVA) (center of gravity of the head-C7 SVA), and (4) C7 slope. Outcomes were evaluated using the Japanese Orthopedic Association scoring system for cervical myelopathy (C-JOA score), neck pain visual analog scale, and neck disability index (NDI). RESULTS: There were no significant differences in patient demographics between the two groups. Postoperatively, C2-7 angle, local angle, cervical SVA, C7 slope, C-JOA score, and neck pain and NDI scores were not significantly different between the two groups; however, the recovery rate of the C-JOA score was superior in the ACDF group (57.5%) compared to the S-LAMP group (42.1%). The recovery rate of the C-JOA score in the local lordosis subgroup (local angle ≥ 0°) showed no significant difference between the two surgical groups. However, in the local kyphosis subgroup (local angle < 0°), C-JOA score recovery rate was worse after S-LAMP (20.4%) than ACDF (57.9%); local angle also worsened postoperatively after S-LAMP. CONCLUSIONS: In patients with local lordosis at the segments of cervical spondylosis and spinal cord compression, S-LAMP showed equivalent surgical outcomes (neurological recovery, neck pain and NDI scores, and cervical alignment) to ACDF. However, in patients with local kyphosis, S-LAMP worsened the kyphosis and resulted in worse neurological recovery.

Multiple and early hyperbaric oxygen treatments enhance muscle healing after muscle contusion injury: a pilot study.

BACKGROUND: The optimal timing of hyperbaric oxygen (HBO2) treatments for the best recovery following muscle injury has yet to be determined. Thus, the optimal number and timing of HBO2 treatments for maximal muscle regeneration were explored. METHODS: The HBO2 treatment protocol consisted of 2.5 ATA 100% oxygen for 120 minutes. Muscle-injured rats were randomized to one of 10 groups: single HBO2 treatment immediately after injury (HBO 1T day 0), one day (HBO 1T day 1), three days (HBO 1T day 3) and five days (HBO 1T day 5) after injury; three HBO2 treatments from immediately after injury to two days after injury (HBO 3T day 0-2), from one to three days after injury (HBO 3T day 1-3), from three to five days after injury (HBO 3T day 3-5), from five to seven days after injury (HBO 3T day 5-7); five daily HBO2 treatments (HBO 5T); and no treatment (NT). RESULTS: HBO 5T and HBO 3T day 0-2, days 1-3 and days 3-5 significantly promoted CD206-positive cell infiltration, satellite cell differentiation and muscle regeneration compared to the NT group. CONCLUSION: Five HBO2 treatments and three HBO2 treatments within three days of injury promote muscle regeneration.

Laminar Closure in Double-door Laminoplasty for Cervical Spondylotic Myelopathy with Nonkyphotic Alignment.

STUDY DESIGN: A retrospective case series. OBJECTIVE: The aim of this study was to investigate the incidence and clinical features of laminar closure in patients with cervical spondylotic myelopathy (CSM) based on prospectively collected data. SUMMARY OF BACKGROUND DATA: Laminar closure after single open-door laminoplasty (LAMP) has been reported to result in poor clinical outcomes. However, no studies to date have examined the underlying mechanisms and frequency of laminar closure after double-door LAMP. METHODS: This study prospectively enrolled 128 consecutive patients with CSM scheduled for double-door LAMP without a laminar spacer at our hospital between 2008 and 2013. Sagittal parameters including C2-7 angle, T1 slope, and cervical sagittal vertical axis (C-SVA), which is defined as the distance between the anterior margin of the external auditory canal plumb line and the posterior-cranial corner of the C7 vertebral body on x-ray, were calculated before and after the operation. Laminar angle was also measured on magnetic resonance images preoperatively and at 1 week and 1 year postoperatively. Laminar closure was defined as > 20% decrease in laminar angle at 1 year compared with that at 1 week postoperatively. The Japanese Orthopedic Association score for cervical myelopathy and the recovery rate determined from the preoperative and postoperative scores were evaluated as clinical outcomes. RESULTS: In total, 110 patients were completely followed up for at least 1 year (follow-up rate: 85.9%). Laminar closure was observed in six cases (5.5%) at the 1-year follow-up. The recovery rate in these six cases was significantly lower than in cases without laminar closure (16.6% vs. 45.1%, respectively). Logistic regression analysis revealed age and C-SVA as significant risk factors for postoperative laminar closure. CONCLUSION: This study is the first to investigate the incidence of laminar closure after double-door LAMP without a laminar spacer. Laminar closure occurred exclusively in elderly patients with kyphotic deformity after LAMP.Level of Evidence: 4.

A Prospective Cohort Study of Dysphagia After Subaxial Cervical Spine Surgery.

STUDY DESIGN: Prospective observational cohort study. OBJECTIVE: To prospectively examine dysphagia after subaxial cervical spine surgery. SUMMARY OF BACKGROUND DATA: Although dysphagia after anterior cervical spine surgery is common and well-studied, it has rarely been examined in posterior subaxial cervical spine surgery. METHODS: This study analyzed 191 consecutive patients (132 male, 59 female; mean age, 64.9 yrs) who underwent subaxial cervical spine surgery for degenerative disease and completed 1 year of follow-up. Anterior decompression with fusion (ADF) was performed in 87 patients, posterior decompression with fusion (PDF) in 21, and laminoplasty (LAMP) in 83. Dysphagia was evaluated by a self-administered questionnaire using the Bazaz dysphagia scale before, 6 months, and 1 year after surgery. Diagnosis, levels and number of operative segments, C2-7 lordotic angle (CL), O-C2 angle (OC2A), C2-7 range of motion (ROM), Japanese Orthopedic Association for cervical myelopathy (C-JOA) score, and neck pain visual analog scale (VAS) were examined. RESULTS: Thirty-two patients (16.8%) reported dysphagia before surgery. New dysphagia after surgery, defined as more than or equal to 1 grade worsening of the Bazaz score after surgery compared with the preoperative status, was observed in 38 patients (19.9%) at 6 months and 32 patients (16.8%) at 1 year. The incidence of new dysphagia at 1 year was 25.3% in the ADF group, 23.8% in the PDF group, and 6.0% in the LAMP group. Fusion surgery (ACDF or PDF) and increased CL after surgery were found as risk factors at 1 year in multivariate analysis; receiver operating characteristic analysis determined a postsurgical change in CL cutoff of 5°. CONCLUSION: Fusion surgery and increased CL after surgery were risk factors for development of dysphagia after subaxial cervical spine surgery. Cervical alignment change due to anterior and posterior fusion surgery can cause postoperative dysphagia.Level of Evidence: 3.

A novel PAI-1 inhibitor prevents ageing-related muscle fiber atrophy.

Sarcopenia is among the most common medical problems of the aging population worldwide and a major social concern. Here, we explored the therapeutic potential of TM5484, a novel orally available PAI-1 inhibitor, to prevent sarcopenia. The sarcopenic phenotypes of the calf muscle of 12- and 6-month-old middle-aged mice were compared. Although significant decline of isometric gastrocnemius muscle force was detected in the older untreated mice, those administered TM5484 had significantly greater calf muscle force, as determined using isometric measurements by electrical stimulation. Histological analysis indicated that cross-sectional gastrocnemius muscle fibers in untreated older mice were thinner than those in younger mice; however, TM5484-treated group showed thicker fibers than younger mice. Treatment with TM5484 for 6 months enhanced Igf1, Atrogin-1, Mt-Co1, and Chrna1 mRNA expression in the mice gastrocnemius muscle, with increased serum IGF-1 concentration. TM5484 induced dose-dependent Igf1, Atrogin-1, and Chrna1 expression in C2C12 myoblastic cells, confirming cell autonomous effect. Further, the presence of plasmin for 72 h caused significantly increased Igf1 expression in C2C12 cells. These findings suggest that oral PAI-1 inhibitors represent a promising therapeutic candidate for preventing sarcopenia progression in humans.

Characterization of a novel compound that promotes myogenesis via Akt and transcriptional co-activator with PDZ-binding motif (TAZ) in mouse C2C12 cells.

Transcriptional co-activator with PDZ-binding motif (TAZ) plays versatile roles in the regulation of cell proliferation and differentiation. TAZ activity changes in response to the cellular environment such as mechanic and nutritional stimuli, osmolarity, and hypoxia. To understand the physiological roles of TAZ, chemical compounds that activate TAZ in cells are useful as experimental reagents. Kaempferol, TM-25659, and ethacridine are reported as TAZ activators. However, as each TAZ activator has a distinct property in cellular functions, additional TAZ activators are awaiting. We screened for TAZ activators and previously reported IB008738 as a TAZ activator that promotes myogenesis in C2C12 cells. In this study, we have characterized IBS004735 that was obtained in the same screening. IBS004735 also promotes myogenesis in C2C12 cells, but is not similar to IBS008738 in the structure. IBS004735 activates TAZ via Akt and has no effect on TAZ phosphorylation, which is the well-described key modification to regulate TAZ activity. Thus, we introduce IBS004735 as a novel TAZ activator that regulates TAZ in a yet unidentified mechanism.

VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration.

Hyperbaric oxygen (HBO) treatment promotes early recovery from muscle injury. Reactive oxygen species (ROS) upregulation is a key mechanism of HBO, which produces high O2 content in tissues through increased dissolution of oxygen at high pressure. Nitric oxide (NO), a type of ROS, generally stabilizes hypoxia-inducible factor (HIF) 1α and stimulates secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) from endothelial cells and macrophages, which then induces angiogenesis. The purpose of the present study was to investigate whether HBO could promote angiogenesis via induction of NO and induce muscle regeneration in contused rat skeletal muscles. The HBO protocol consisted of 2.5 atmospheres absolute (ATA) 100% oxygen for 120 minutes, once a day for 5 consecutive days. We also evaluated the effects of a ROS inhibitor (NAC) or NOS-specific inhibitor (L-NAME) on HBO. HBO significantly increased NO3-, VEGF, and bFGF levels and stabilized HIF1α within 1 day. HBO promoted blood vessel formation at 3-7 days and muscle healing at 5-7 days after contusion. Administration of both NAC and L-NAME before HBO suppressed angiogenesis and muscle regeneration even after HBO. HBO thus promoted angiogenesis and muscle regeneration mainly through generation of NO in the early phase after muscle contusion injury.

Retrospective analysis of surgical outcomes for atlantoaxial subluxation.

BACKGROUND: Atlantoaxial subluxation (AAS) is characterized by excessive movement at the junction between the atlas (C1) and axis (C2) as a result of either a bony or ligamentous abnormality. Surgical intervention is a therapeutic choice for AAS. In addition to C1 laminectomy (LAM), surgical fixation for subluxation or instability is performed by various techniques. While surgical treatment options for AAS have increased, the outcomes of different surgical techniques remain unclear. METHODS: The authors conducted a retrospective analysis of the outcomes of 30 consecutive spinal surgeries performed for AAS patients, C1 LAM in 11 cases and C1/2 fixation in 19 cases. We investigated the correlation between the clinical outcomes and the surgical methods. We also examined the factors related to poor outcomes (the recovery rate of the Japanese Orthopedic Association score for cervical myelopathy < 40%) following AAS surgeries. RESULTS: From a surgical method perspective, the patients in the C1 LAM group were older than those in the C1/2 fixation group (74.6 years vs 68.0 years), and the average recovery rate from the preoperative status was as follows: the C1 LAM group, 39.4%; the C1/2 fixation group, 49.8%. The C-JOA score was significantly improved after surgery in the C1/2 fixation group (from 9.8 to 13.1 points). The fixation technique seemed to successfully reduce C1/2 displacement. Each group exhibited a slight increase in the C1/2 angle and a decrease in the C2-7 angles after the operation. A higher preoperative atlantodental interval (ADI) was associated with good outcomes after the C1/2 fixation. The postoperative ADI was significantly reduced from 8.6 mm to 3.8 mm in the good outcome group after fixation. Patients with higher C1/2 angle showed good outcomes after C1 LAM. Despite the good neurological improvement, the C1/2 fixation method showed higher complication rates compared with C1 LAM method. CONCLUSIONS: The results of this study showed that the C1/2 fixation technique exhibited effectiveness in terms of neurological recovery. However, there was a high complication rate in surgeries for AAS, especially in the C1/2 fixation. C1 LAM would be considered for high-risk AAS cases such as elderly patients with multiple comorbidities.

A case-control questionnaire survey of decompression sickness risk in Okinawa divers.

BACKGROUND: Decompression sickness (DCS) is a rare condition that is often difficult to diagnose in deep-sea divers. Because of this, prevention and early diagnosis are important. In this case-control study, we examined the risk and preventive factors associated with DCS. METHODS: Our original questionnaire survey was conducted among 269 recreational divers in Okinawa. Divers who were diagnosed with DCS by a physician (n = 94) were compared with healthy recreational divers (n = 175). The questionnaire consisted of 30 items and included a dive profile. Odds ratios and multiple logistic regression analysis were used to estimate the relative risk of DCS. RESULTS: Logistic regression analysis revealed the following risk factors for DCS: a past history of DCS, drinking alcohol the evening before diving, indicating decompression stops, cold exposure after the dive, and maximum depth. Preventive factors included hydration before the dive, deep stops, safety stops and using nitrox gas. The results were reliable according to the Hosmer-Lemeshow and omnibus tests. CONCLUSION: We identified certain risk factors, together with their relative risks, for DCS. These risk factors may facilitate prevention of DCS among Okinawa divers.

Hyperbaric oxygen reduces inflammation, oxygenates injured muscle, and regenerates skeletal muscle via macrophage and satellite cell activation.

Hyperbaric oxygen treatment (HBO) promotes rapid recovery from soft tissue injuries. However, the healing mechanism is unclear. Here we assessed the effects of HBO on contused calf muscles in a rat skeletal muscle injury model. An experimental HBO chamber was developed and rats were treated with 100% oxygen, 2.5 atmospheres absolute for 2 h/day after injury. HBO reduced early lower limb volume and muscle wet weight in contused muscles, and promoted muscle isometric strength 7 days after injury. HBO suppressed the elevation of circulating macrophages in the acute phase and then accelerated macrophage invasion into the contused muscle. This environment also increased the number of proliferating and differentiating satellite cells and the amount of regenerated muscle fibers. In the early phase after injury, HBO stimulated the IL-6/STAT3 pathway in contused muscles. Our results demonstrate that HBO has a dual role in decreasing inflammation and accelerating myogenesis in muscle contusion injuries.

Elimination of CT-detected gas bubbles derived from decompression illness with abdominal symptoms after a short hyperbaric oxygen treatment in a monoplace chamber: a case report.

We report the case of a 54-year-old male compressed-air worker with gas bubbles detected by computed tomography (CT). He had complained of strong abdominal pain 30 minutes after decompression after working at a pressure equivalent to 17 meters of sea water for three hours. The initial CT images revealed gas bubbles in the intrahepatic portal vein, pulmonary artery and bilateral femoral vein. After the first hyperbaric oxygen treatment (HBO2 at 2.5 atmospheres absolute/ATA for 150 minutes), no bubbles were detected on repeat CT examination. The patient still exhibited abdominal distension, mild hypesthesia and slight muscle weakness in the upper extremities. Two sessions of U.S. Navy Treatment Table 6 (TT6) were performed on Days 6 and 7 after onset. The patient recovered completely on Day 7. This report describes the important role of CT imaging in evaluating intravascular gas bubbles as well as eliminating the diagnosis of other conditions when divers or compressed-air workers experience uncommon symptoms of decompression illness. In addition, a short treatment table of HBO2 using non-TT6 HBO2 treatment may be useful to reduce gas bubbles and the severity of decompression illness in emergent cases.

Hyperbaric oxygen therapy for a refractory skin ulcer after radical mastectomy and radiation therapy: a case report.

BACKGROUND: Radiation therapy is performed as an adjuvant therapy when indicated following surgical resection of malignant tumors. However, radiation exposure induces acute or chronic dermatitis, depending on the radiation dose, interval, tissue volume, or irradiated area of the body. Radiation-induced skin ulcers and osteomyelitis of the underlying bone are intractable late-stage complications of radiation therapy, and often require reconstructive surgery to cover exposed tissue. Hyperbaric oxygen therapy has been suggested as a treatment for delayed radiation injury with soft tissue and bony necrosis. CASE PRESENTATION: A 74-year-old Japanese female underwent left radical mastectomy for breast cancer (T3N3M0, stage IIIB) in 1987. Radiation therapy was initiated 6 weeks after the surgery. She received telecobalt-60 in a total dose of 50 Gy with 25 fractions to the left supraclavicular, parasternal and left axillary regions, and electron treatment (9 MeV) in a total dose of 50 Gy in 25 fractions to the left chest wall. After irradiation, her skin became thinner and more fragile on the left chest wall, but no severe infections were observed. She noticed a small ulcer that repeatedly healed and recurred in 2000. She visited the hospital where she received radiation therapy and was treated for a skin ulcer on the left chest wall in December 2012. A fistula developed and then pus was discharged in January 2013. She was referred to the hyperbaric medical center in February 2013, and the fistula (1.5 × 3 cm) with pus discharge was observed. She was diagnosed with a late-onset radiation-induced skin ulcer that developed 25 years after radical mastectomy. HBO2 (2.5 atmospheres absolute with 100% oxygen for 60 minutes) was indicated for the refractory ulcer and osteomyelitis of the ribs. The patient was treated with HBO2 a total of 101 times over the course of 1 year and completely recovered. CONCLUSIONS: Hyperbaric oxygen therapy can be performed safely for even more than 100 sessions in patients with radiation-induced skin ulcers and osteomyelitis. Hyperbaric oxygen therapy can be considered as an alternative, conservative treatment when surgical resection for late-onset, radiation-induced skin ulcers is not indicated because of fragile skin in the irradiated areas.

Gene targeting of the transcription factor Mohawk in rats causes heterotopic ossification of Achilles tendon via failed tenogenesis.

Cell-based or pharmacological approaches for promoting tendon repair are currently not available because the molecular mechanisms of tendon development and healing are not well understood. Although analysis of knockout mice provides many critical insights, small animals such as mice have some limitations. In particular, precise physiological examination for mechanical load and the ability to obtain a sufficient number of primary tendon cells for molecular biology studies are challenging using mice. Here, we generated Mohawk (Mkx)(-/-) rats by using CRISPR/Cas9, which showed not only systemic hypoplasia of tendons similar to Mkx(-/-) mice, but also earlier heterotopic ossification of the Achilles tendon compared with Mkx(-/-) mice. Analysis of tendon-derived cells (TDCs) revealed that Mkx deficiency accelerated chondrogenic and osteogenic differentiation, whereas Mkx overexpression suppressed chondrogenic, osteogenic, and adipogenic differentiation. Furthermore, mechanical stretch stimulation of Mkx(-/-) TDCs led to chondrogenic differentiation, whereas the same stimulation in Mkx(+/+) TDCs led to formation of tenocytes. ChIP-seq of Mkx overexpressing TDCs revealed significant peaks in tenogenic-related genes, such as collagen type (Col)1a1 and Col3a1, and chondrogenic differentiation-related genes, such as SRY-box (Sox)5, Sox6, and Sox9 Our results demonstrate that Mkx has a dual role, including accelerating tendon differentiation and preventing chondrogenic/osteogenic differentiation. This molecular network of Mkx provides a basis for tendon physiology and tissue engineering.

The facilitatory effects of hyperbaric oxygen treatment on membrane bone wound healing in a rat calvarial defect model.

We examined the effect of hyperbaric oxygen (HBO2) treatment on bone wound healing in a rat calvarial defect. Critical-sized defects were created in the calvaria of adult Wistar rats. The animals were divided into four groups--HBO2, normobaric oxygen, hyperbaric air, and no treatment. Treatments were performed five days a week, for two weeks. Micro-computerized tomography and histological analysis were used to evaluate the bone defects. Regenerated bone areas were calculated as the percentage of new bone in the cross-sectional area of defect. The new bone cross-sectional area was significantly greater in the HBO2 group than in the other groups. There were no significant differences in the numbers of nucleated cells in the new bone areas. Although new bone volume per defect volume was significantly greater in the HBO2 group than in the other groups, no significant differences in bone mineral density in the new bone area were observed. These findings indicate the facilitatory role of HBO2 treatment on bone wound healing in the rat calvarial bone defect, and it does not appear to have any negative effects on bone maturity. We propose that HBO2 treatment would be useful in promoting bone regeneration following injury in the orofacial region.