Investigation of the Relationship between Surface Features, Protein Adsorption, and Osteoimmunomodulation: The Case of a Chemically Treated Titanium Alloy.

This paper deals with the combined effects of immune response and osseointegration because of the lack of comprehensive studies on this topic. An antibacterial Ti surface was considered because of the high risk of infection for titanium bone implants. A chemically treated Ti6Al4 V alloy [Ti64(Sr-Ag)] with a microporous and Sr-Ag doped surface was compared to a polished version (Ti64) regarding protein adsorption (albumin and fibronectin) and osteoimmunomodulation. Characterization via fluorescence microscopy and zeta potential showed a continuous fibronectin layer on Ti64(Sr-Ag), even with preadsorbed albumin, while it remained filamentous on Ti64. Macrophages (differentiated from THP-1 monocytes) were cultured on both surfaces, with viability and cytokine release analyzed. Differently from Ti64, Ti64(Sr-Ag) promoted early anti-inflammatory responses and significant downregulation of VEGF. Ti64(Sr-Ag) also enhanced human bone marrow mesenchymal cell differentiation toward osteoblasts, when a macrophage-conditioned medium was used, influencing ALP production. Surface properties in relation to protein adsorption and osteoimmunomodulation were discussed.

Genetic parameters for conception rate and milk production traits within and across Holstein herds with different housing types and feeding systems during the first 3 lactations.

The housing types (HST) in which dairy cows are kept and the feeding systems (FDS) used differ among farmers in Japan. Here, we investigated the genetic relationships among conception rate at first insemination (CR) and milk production traits (PROD) during the first 3 lactations of Holstein cows by using a multiple-trait model that considered the trait values of herds with different HST [tiestall (TSL) barn, freestall (FS) barn, or grazing (GZ)] and FDS as separate traits. Milk production and conception records of Holstein cows in the Hokkaido region of Japan (283,611 records for first lactation, 253,902 for second, and 181,197 for third) were analyzed. We categorized herds with TSL or FS into 2 types of FDS for cows: separate feeding (SF) of roughage plus concentrate or feeding of total mixed ration, in which roughage and concentrates were mixed before feeding. The PROD analyzed were cumulative milk, fat, and protein yields within 305 d and lactation persistency, which we defined as the difference between milk yields at 240 and 60 d in milk. We estimated the heritabilities for CR or PROD within each HST or HST × FDS group and the genetic correlations between these traits within each group or across different groups within each lactation by using a 3-HST (TSL, FS, and GZ) × 2-trait (CR and each PROD) or 2-HST (TSL and FS) × 2-FDS × 2-trait animal model. Heritability estimates for CR in GZ were higher than those in TSL or FS, and genetic correlations for CR between GZ and TSL or FS barns were weaker than those between TSL and FS barns. In addition, genetic correlations between CR and PROD in GZ were weaker than those in TSL and FS barns. In the comparison among the 4 HST × FDS except GZ, heritability estimates for CR in FS × SF were higher than those in the others, and genetic correlations for CR between FS × SF and the other systems were relatively weak. These results indicated that differences in the production system for Holstein cows influence genotypic effects in terms of the cows' ability to conceive and the genetic relationships between fertility traits and milk production traits.

Analysis of masticatory muscle coordination during unilateral single-tooth clenching using muscle functional magnetic resonance imaging.

In a previous study, we used muscle functional magnetic resonance imaging to show that the anterior movement of the occlusal point increased the activity of the superior head of the ipsilateral lateral pterygoid muscle (ipsilateral SHLP) during unilateral single-tooth clenching. The purpose of this study was to verify the hypothesis that the increased activity of the ipsilateral SHLP described above serves to antagonise the occlusal force acting on the condyle. In total, 9 healthy volunteers were requested to perform left unilateral clenching at the first molar or first premolar region for 1 minute at 20% or 40% maximum voluntary clenching force. Changes in the mean proton transverse relaxation time (∆T2) were examined from the magnetic resonance images obtained before and after each clenching act as an index of the activity in all masticatory muscles. Correlation analyses of the mean ΔT2 for each volume of interest were performed with the first molar or premolar clenches to analyse the correlation between the activities in each muscle. A statistically significant correlation was exhibited between the ipsilateral temporal and ipsilateral SHLP (r = .651, P = .003) during first premolar clenching. However, no significant correlations were observed in the ipsilateral SHLP during first molar clenching. The results of this study suggest that the ipsilateral SHLP may contribute to the pulling of the mandibular condyle forward against the occlusal force generated by the ipsilateral temporal muscle.

Physiological exercise loading suppresses post-traumatic osteoarthritis progression via an increase in bone morphogenetic proteins expression in an experimental rat knee model.

OBJECTIVE: To evaluate the dose-response relationship of exercise loading in the cartilage-subchondral bone (SB) unit in surgically-induced post-traumatic osteoarthritis (PTOA) of the knee. DESIGN: Destabilized medial meniscus (DMM) surgery was performed on the right knee of 12-week-old male Wistar rats, and sham surgery was performed on the contralateral knee. Four weeks after the surgery, the animals were subjected to moderate (12 m/min) or intense (21 m/min) treadmill exercises for 30 min/day, 5 days/week for 4 weeks. PTOA development in articular cartilage and SB was examined using histological and immunohistochemical analyses, micro-computed tomography (micro-CT) analysis, and biomechanical testing at 8 weeks after surgery. Gremlin-1 was injected to determine the role of bone morphogenetic protein (BMP) signaling on PTOA development following moderate exercise. RESULTS: Moderate exercise increased BMP-2, BMP-4, BMP-6, BMP receptor 2, pSmad-5, and inhibitor of DNA binding protein-1 expression in the superficial zone chondrocytes and suppressed cartilage degeneration, osteophyte growth, SB damage, and osteoclast-mediated SB resorption. However, intense exercise had little effect on BMP expression and even caused progression of these osteoarthritis (OA) changes. Gremlin-1 injection following moderate exercise caused progression of the PTOA development down to the level of the non-exercise DMM-operated knee. CONCLUSIONS: Exercise regulated cartilage-SB PTOA development in DMM-operated knees in a dose-dependent manner. Our findings shed light on the important role of BMP expression in superficial zone chondrocytes in attenuation of PTOA development following physiological exercise loading. Further studies to support a mechanism by which BMPs would be beneficial in preventing PTOA progression are warranted.

A randomized controlled phase II clinical trial comparing ONO-4053, a novel DP1 antagonist, with a leukotriene receptor antagonist pranlukast in patients with seasonal allergic rhinitis.

BACKGROUND: Prostaglandin D2 (PGD2 ) is primarily produced by mast cells and is contributing to the nasal symptoms including nasal obstruction and rhinorrhea. OBJECTIVE: This study aimed to evaluate the efficacy and safety of a novel PGD2 receptor 1 (DP1) antagonist, ONO-4053, in patients with seasonal allergic rhinitis (SAR). METHODS: This study was a multicenter, randomized, double-blind, parallel-group study of patients with SAR. Following a one-week period of placebo run-in, patients who met the study criteria were randomized to either the ONO-4053, leukotriene receptor antagonist pranlukast, or placebo group for a two-week treatment period. A total of 200 patients were planned to be randomly assigned to receive ONO-4053, pranlukast, or placebo in a 2:2:1 ratio. Nasal and eye symptoms were evaluated. RESULTS: Both ONO-4053 and pranlukast had higher efficacy than placebo on all nasal and eye symptoms. ONO-4053 outperformed pranlukast in a total of three nasal symptom scores (T3NSS) as well as in individual scores for sneezing, rhinorrhea, and nasal itching. For T3NSS, the Bayesian posterior probabilities that pranlukast was better than placebo and ONO-4053 was better than pranlukast were 70.0% and 81.6%, respectively, suggesting that ONO-4053 has a higher efficacy compared with pranlukast. There was no safety-related issue in this study. CONCLUSIONS: We demonstrated that the efficacy of ONO-4053 was greater than that of pranlukast with a similar safety profile. This study indicates the potential of ONO-4053 for use as a treatment for SAR (JapicCTI-142706).

Cost-effectiveness of cognitive remediation and supported employment for people with mental illness: a randomized controlled trial.

BACKGROUND: Little is known about the economic benefits of cognitive remediation and supported employment (CR + SE). The present study aimed to investigate the cost-effectiveness of CR + SE compared with traditional vocational services (TVS). METHOD: Individuals with mental illness and low cognitive function were recruited at six sites in Japan. A total of 111 participants were randomly allocated to the CR + SE group or the TVS group. Clinical and vocational outcomes were assessed at baseline and 12-month follow-up. Service utilization data were collected monthly. The data on outcomes and costs were combined to examine cost-effectiveness. RESULTS: The data were obtained from a total of 92 participants. The CR + SE group resulted in better vocational and clinical outcomes (employment rate, 62.2%; work tenures, 78.6 days; cognitive improvement, 0.5) than the TVS group (19.1%, 24.9 days and 0.2). There was no significant difference in mean total costs between the groups (CR + SE group: $9823, s.d. = $6372, TVS group: $11 063, s.d. = $11 263) with and without adjustment for covariates. However, mean cost for medical services in the CR + SE group was significantly lower than that in the TVS group after adjusting covariates (Β = -$3979, 95% confidence interval -$7816 to -$143, p = 0.042). Cost-effectiveness acceptability curves for vocational outcomes illustrated the high probabilities (approximately 70%) of the CR + SE group being more cost-effective than TVS when society is not willing to pay additional costs. CONCLUSIONS: CR + SE appears to be a cost-effective option for people with mental illness who have low cognitive functioning when compared with TVS.

Arc expression identifies the lateral amygdala fear memory trace.

Memories are encoded within sparsely distributed neuronal ensembles. However, the defining cellular properties of neurons within a memory trace remain incompletely understood. Using a fluorescence-based Arc reporter, we were able to visually identify the distinct subset of lateral amygdala (LA) neurons activated during auditory fear conditioning. We found that Arc-expressing neurons have enhanced intrinsic excitability and are preferentially recruited into newly encoded memory traces. Furthermore, synaptic potentiation of thalamic inputs to the LA during fear conditioning is learning-specific, postsynaptically mediated and highly localized to Arc-expressing neurons. Taken together, our findings validate the immediate-early gene Arc as a molecular marker for the LA neuronal ensemble recruited during fear learning. Moreover, these results establish a model of fear memory formation in which intrinsic excitability determines neuronal selection, whereas learning-related encoding is governed by synaptic plasticity.

Exercise intervention increases expression of bone morphogenetic proteins and prevents the progression of cartilage-subchondral bone lesions in a post-traumatic rat knee model.

OBJECTIVE: This study aimed to determine whether treadmill walking (TW) prevents the progression of post-traumatic osteoarthritic changes in cartilage-subchondral bone unit, and whether the exercise timing changes the exercise efficacy in destabilized medial meniscus (DMM) rat knees. DESIGN: Twelve-week-old male Wistar rats underwent DMM surgery on their right knees and sham surgery on their left knees and were assigned to either the sedentary (n = 10) or walking (n = 24) groups. The rats in the walking group were subjected to TW from day 2 through 4 weeks, from 4 through 8 weeks, or from day 2 through 8 weeks (n = 8 per group). Osteoarthritic changes of cartilage and subchondral bone were assessed with micro-computed tomography, histology, and immunohistochemistry 8 weeks after surgery. RESULTS: TW prevented the progression of cartilage and subchondral bone lesions induced by the DMM, and increased bone morphogenetic protein (BMP)-2 and -6 expressions in superficial zone chondrocytes and bone-lining cells including osteoblasts. Furthermore, the TW-induced increase in BMPs varied with the exercise timing. Beginning TW 4 weeks after DMM surgery was the best option for increasing BMPs, coinciding with the most robust prevention of osteoarthritic changes. CONCLUSIONS: TW increased the expression of BMPs and prevented the progression of cartilage-subchondral bone lesions in rat knees with a DMM. Selective exercise timing may be a key factor in the development of an exercise regimen for preventing the progression of post-traumatic osteoarthritis (PTOA). Furthermore, exercise may have favorable effects even after the PTOA has been developed.

Subchondral plate porosity colocalizes with the point of mechanical load during ambulation in a rat knee model of post-traumatic osteoarthritis.

OBJECTIVE: This study investigated the association between spatiotemporal cartilage-subchondral bone plate alterations and mechanical load during ambulation in an experimental rat model of destabilized medial meniscus (DMM). DESIGN: Twelve-week-old Wistar rats (n = 38) underwent DMM surgery on the right knee and sham surgery on the left knee. At 2 and 4 weeks after surgery, subchondral bone changes were evaluated via micro-computed tomography with various knee flexion angles to simulate weight-bearing during rat ambulation under a 3-dimensional motion capture apparatus. Additionally, the biomechanical properties, histology, and ultrastructure of the medial tibia and femoral condyle were evaluated. RESULTS: Focal subchondral bone plate perforations were confirmed in the medial tibia within 2 weeks after surgery and were aggravated rapidly 2 weeks later. This subchondral plate porosity colocalized with articular cartilage lesions as confirmed by histology and scanning electron microscopy, and coincided with the likely point of contact between the posterior femoral condyle and tibial plateau during ambulation. Biomechanical properties were confirmed at the medial tibia, at which stiffness was reduced to approximately half that of the sham-operated knee at 4 weeks after surgery. CONCLUSIONS: Cartilage-subchondral bone plate alterations localized in the region of the point of mechanical load during ambulation in DMM-operated knees, at which the mechanical integrity of cartilage was impaired. These results indicate that DMM-induced increases in mechanical load play an important role in the pathogenesis of early post-traumatic osteoarthritis (OA), and it might accelerate the development of the disease via cartilage-subchondral bone plate crosstalk through increased subchondral plate perforations.

C-reactive protein levels are associated with cerebral small vessel-related lesions.

OBJECTIVE: Inflammation has received increasing attention as a cause of stroke. Although several lines of evidence suggest that inflammatory processes have a role in arteriosclerotic vascular events, their involvement remains to be determined. The purpose of this study was to examine the associations between serum high-sensitive C-reactive protein (hs-CRP) levels and cerebral small vessel (CSV)-related lesions as a manifestation of arteriosclerosis. MATERIALS AND METHODS: Neurologically normal subjects without any history of neurologic or psychiatric diseases were enrolled (n = 519). All the participants underwent magnetic resonance imaging (MRI), and their CSV-related lesions (i.e., lacunar infarcts, cerebral microbleeds, deep white matter hyperintensity, and periventricular hyperintensity) were evaluated. The serum levels of hs-CRP were evaluated as common inflammatory markers. RESULTS: Subjects with higher C-reactive protein (CRP) levels had more lacunar infarcts (P = 0.02). After adjusting for the traditional cardiovascular risk factors, higher hs-CRP levels were still associated with the presence of lacunar infarcts [odds ratio for the highest vs the lowest tertile of hs-CRP, 3.57 (95% confidence interval: 1.30-9.80)]. These associations did not change when the logarithmically transformed values for hs-CRP were included. Furthermore, subjects with higher CRP levels had more cerebral microbleeds (P = 0.03), more severe deep white matter hyperintensity (P = 0.04), and periventricular hyperintensity (P = 0.04); however, these associations were not observed after adjusting for the cardiovascular risk factors. CONCLUSIONS: Higher levels of hs-CRP were associated with lacunar infarcts. Thus, inflammatory processes may be involved in the pathogenesis of small-vessel disease.

Evaluation of masticatory activity during unilateral single tooth clenching using muscle functional magnetic resonance imaging.

Masticatory muscle activity during teeth clenching is affected by occlusal pattern. However, few studies have performed simultaneous evaluation of all masticatory activities during teeth clenching under various occlusal conditions. The aim of this study was to use muscle functional magnetic resonance imaging (mfMRI) to evaluate the effects of changes in occlusal point on masticatory activity during single tooth clenching. Changes in mean proton transverse relaxation time (∆T2) as an index of activity in all masticatory muscles during left unilateral clenching at the first molar or first premolar for 1 min were examined in nine healthy volunteers. Bite force was maintained at 40% of the maximum voluntary clenching force. The ∆T2 values of the masseter and lateral pterygoid muscles were analysed separately for superficial and deep layers, and for superior and inferior heads. The ∆T2 values for the ipsilateral deep masseter were significantly lower, and for the superior head of the ipsilateral lateral pterygoid muscles were significantly higher, after left first premolar clenching compared to left first molar clenching. These results quantitatively demonstrate a significant increase in activity of the superior head of the ipsilateral lateral pterygoid muscle and a significant decrease in activity of the ipsilateral deep masseter muscle with forward displacement of the occlusal contact point during unilateral tooth clenching.

Effects of short-term gentle treadmill walking on subchondral bone in a rat model of instability-induced osteoarthritis.

OBJECTIVE: Subchondral bone cyst (SBC) growth, caused by osteoclast activity during early knee osteoarthritis (OA) pathogenesis, should be treated to prevent further progressions of OA. In the present study, we evaluated the effects of gentle treadmill walking on subchondral bone and cartilage changes in an experimental rat model of destabilized medial meniscus (DMM). METHOD: Twelve-week-old Wistar rats underwent DMM surgery in their right knee and sham surgery in their left knee and were assigned to either the sedentary group or walking group (n = 42/group). Animals in the walking group were subjected to treadmill exercise 2 days after surgery, which included walking for 12 m/min, 30 min/day, 5 days/week for 1, 2, and 4 week(s). Subchondral bone and cartilage changes were evaluated by micro-CT analysis, histological analysis, and biomechanical analysis. RESULTS: Treadmill walking had a tendency to suppress SBC growth, which was confirmed by micro-CT (P = 0.06) and positive staining for tartrate-resistant acid phosphatase (TRAP) activity for the osteoclast number per bone surface (P = 0.09) 4 weeks after surgery. These changes coincide with the prevention of cartilage degeneration as evaluated by the Osteoarthritis Research Society International (OARSI) score (P < 0.05) and biomechanically softening (P < 0.05). Furthermore, treadmill walking could suppressed increasing osteocyte deaths (P < 0.01), which was positively correlated with the OARSI score (r = 0.77; P < 0.01). CONCLUSION: These results indicate biomechanical and biological links exist between cartilage and subchondral bone; preventive effects of treadmill walking on subchondral bone deterioration might be partly explained by the chondroprotective effects.

Utility of T2 mapping and dGEMRIC for evaluation of cartilage repair after allograft chondrocyte implantation in a rabbit model.

OBJECTIVE: To investigate the effectiveness of quantitative Magnetic resonance imaging (MRI) for evaluating the quality of cartilage repair over time following allograft chondrocyte implantation using a three-dimensional scaffold for osteochondral lesions. DESIGN: Thirty knees from 15 rabbits were analyzed. An osteochondral defect (diameter, 4 mm; depth, 1 mm) was created on the patellar groove of the femur in both legs. The defects were filled with a chondrocyte-seeded scaffold in the right knee and an empty scaffold in the left knee. Five rabbits each were euthanized at 4, 8, and 12 weeks and their knees were examined via macroscopic inspection, histological and biochemical analysis, and quantitative MRI (T2 mapping and dGEMRIC) to assess the state of tissue repair following allograft chondrocyte implantation with a three-dimensional scaffold for osteochondral lesions. RESULTS: Comparatively good regenerative cartilage was observed both macroscopically and histologically. In both chondrocyte-seeded and control knees, the T2 values of repair tissues were highest at 4 weeks and showed a tendency to decrease with time. ΔR1 values of dGEMRIC also tended to decrease with time in both groups, and the mean ΔR1 was significantly lower in the CS-scaffold group than in the control group at all time points. ΔR1 = 1/r (R1post - R1pre), where r is the relaxivity of Gd-DTPA(2-), R1 = 1/T1 (longitudinal relaxation time). CONCLUSION: T2 mapping and dGEMRIC were both effective for evaluating tissue repair after allograft chondrocyte implantation. ΔR1 values of dGEMRIC represented good correlation with histologically and biochemically even at early stages after the implantation.

Hidden osteophyte formation on plain X-ray is the predictive factor for development of knee osteoarthritis after 48 months--data from the Osteoarthritis Initiative.

OBJECTIVE: To examine whether the detection of osteophytes anywhere in the knee could serve as a pre-radiographic biomarker for osteoarthritis (OA) development. METHODS: Baseline magnetic resonance imaging (MRIs) of 132 participants in the Osteoarthritis Initiative (OAI) were studied. Based on radiographs, 66 knees were assessed as osteoarthritis-free (no-osteoarthritis [NOA], or Kellgren/Lawrence [K/L] severity grade 0/1 both at baseline and 48 months), and another 66 knees were assessed as having radiographic OA changes (pre-radiographic osteoarthritis [PROA], or with K/L grade 0/1 at baseline and grade ≥ 2 at 48 months). Using baseline MRI data, we examined eight sites of osteophyte formation: the medial and lateral femoral condyle (MFC and LFC, respectively); medial and lateral tibial plateau (MTP and LTP, respectively); medial and lateral facets of the patellofemoral joint (PM and PL, respectively); tibial spine (TS); and femoral intercondylar notch (IC). Knee joint osteophyte size was assessed via the 8-point marginal osteophytes item of the whole-organ magnetic resonance imaging score (WORMS). The frequencies and distributions of osteophytes were compared between groups. RESULTS: Mild-size osteophytes (defined as score ≥ 2) were observed more frequently at the MFC (P = 0.00278), MTP (P = 0.0046), TS (P = 0.0146), PM (P < 0.0001), PL (P = 0.0012), and IC (P < 0.0001) in PROA knees than in NOA knees. Moderate-size osteophytes (defined as score ≥ 4) were more frequently observed in PROA knees than in NOA knees only at the IC (P < 0.0001). CONCLUSION: Knees with osteophyte formation at the IC, even those of K/L severity grade 0/1, are at risk for the development of radiographic OA by 48 months.

Genetic epidemiology of tooth agenesis in Japan: a population- and family-based study.

Tooth agenesis is one of the most common congenital anomalies in humans. However, the etiology of tooth agenesis remains largely unclear, as well as evidence base useful for genetic counseling. Therefore, we estimated the prevalence and sibling recurrence risk, and investigated agenetic patterns systematically. Tooth agenesis was classified into two subtypes: hypodontia (one to five missing teeth) and oligodontia (six or more missing teeth). The prevalence of these two subtypes were 6.8% [95% confidence interval (CI): 6.1-7.7%] and 0.1% (95% CI: 0.04-0.3%), respectively, and sibling recurrence risk of these were 24.5% (95% CI: 13.8-38.3%) and 43.8% (95% CI: 26.4-62.3%), respectively. This result suggests that the severe phenotype, oligodontia, might be mostly transmitted in a dominant fashion. Using a simple statistical modeling approach, our data were found to be consistent with a bilateral symmetry model, meaning that there was equal probability of missing teeth from the right and left sides.

Magnetic stimulation and movement-related cortical activity for acute stroke with hemiparesis.

BACKGROUND AND PURPOSE: This double-blind, randomized, placebo-controlled study investigated the beneficial effects of repetitive transcranial magnetic stimulation (rTMS) to patients with motor paresis in acute subcortical stroke on functional recovery and electrophysiological measures. METHODS: Twenty patients with acute stroke were randomized into real rTMS (n = 10) or sham (n = 10) groups. Patients received five daily sessions of rTMS with 1200 pulses at 1 Hz for 20 min or sham stimulation over the contralesional motor cortex. Movement-related cortical potential MRCP, consisting of the Bereitschaftpotential, negative slope (NS') and motor potential (MP), was recorded during self-paced wrist extension of the affected limb associated with assessment of the Fugl-Meyer assessment (FMA) of the upper extremity, the pegboard test and the grip strength before and after the rTMS session. RESULTS: Real rTMS improved the FMA and pegboard test scores compared to the sham group in the affected hand. This improvement was associated with increases in the MP and NS' over the front-central sites in the ipsilesional hemisphere, whereas the sham group did not show significant changes in MRCP components by rTMS. CONCLUSIONS: Our findings suggest that low-frequency rTMS to the contralesional motor cortex facilitates functional recovery of paretic limbs in acute stroke patients through enhancing the the neuronal activity of ipsilesional motor and pre-motor areas.

Calcification during bone healing in a standardised rat calvarial defect assessed by micro-CT and SEM-EDX.

OBJECTIVE: The study was designed to investigate the process of calcification during bone healing in a standardized rat calvarial bone defect model, measured by bone mineral density and the concentrations and distributions of calcium, phosphorus and carbon in the bone matrix. MATERIALS AND METHODS: A standard defect was made on the parietal bone of 12-week-old rats under anaesthesia. The rats were fixed in weeks 1, 2, 4 and 8,and the calvaria were resected and examined with microcomputed tomography, then frozen and sectioned for histology and analysed with energy-dispersive X-ray spectroscopy (EDX). Parietal bone of 12-week-old control rats was processed similarly. RESULTS: The mineral density of healing bone increased with time. The healing bone became thicker and denser with time in histology. The distributions of Ca and P expanded over the bone matrix, whereas that of C became localised and complemented that of C and P. The Ca/P concentration ratio increased, whereas the C/Ca and C/P ratios decreased in the healing bone matrix. CONCLUSION: Healing bone is immaturely calcified initially and proceeds calcification gradually, that is, as the bone volume increases, mineral increases in density and matures in quality, while organic components decrease.

Development of novel treatment with a bioabsorbable esophageal patch for benign esophageal stricture.

Using a large animal model, we examined whether circumferential stricture after esophageal endoscopic submucosal dissection (ESD) can be treated by grafting a bioabsorbable esophageal patch. Circumferential ESD was performed on the thoracic esophagus in pigs (n = 6) to create a stricture, for which one of the following interventions was performed: (1) the stricture site was longitudinally incised, and an artificial esophageal wall (AEW) was grafted after placing a bioabsorbable stent (AEW patch group, n = 3); (2) endoscopic balloon dilation (EBD) was performed every other week after stricture development (EBD group, n = 3). In both groups, esophageal fluoroscopy was performed 8 weeks after the interventions, and the esophagus was excised for histological examination of the patched site. In the AEW patch group, esophageal fluoroscopy revealed favorable passage through the patched site. Histologically, the mucosal epithelium and lamina propria had regenerated as in the normal area. In the EBD group, the circumferential stricture site showed marked thickening, and there were hypertrophic scars associated with epithelial defects on the luminal surface. Histologically, defects of the mucosal epithelium and full-thickness proliferation of connective tissue were observed. AEW patch grafting was suggested to be a potentially novel treatment strategy for post-ESD esophageal circumferential stricture.

Destabilization of the medial meniscus leads to subchondral bone defects and site-specific cartilage degeneration in an experimental rat model.

OBJECTIVE: This study aimed to investigate subchondral bone changes using micro-computed tomography (micro-CT) and regional differences in articular cartilage degeneration, focusing on changes of cartilage covered by menisci, in the early phase using a destabilization of the medial meniscus (DMM) model. METHOD: The DMM model was created as an experimental rat osteoarthritis (OA) model (12 weeks old; n = 24). At 1, 2, and 4 weeks after surgery, the rats were sacrificed, and knee joints were scanned using a Micro-CT system. Histological sections of the medial tibial plateau, which was divided into inner, middle, and outer regions, were prepared and scored using the modified OARSI scoring system. The cartilage thickness was also calculated, and matrix metalloproteinase 13 (MMP13), Col2-3/4c, and vascular endothelial growth factor (VEGF) expression was assessed immunohistochemically. RESULTS: Subchondral bone defects were observed in the middle region, in which the cartilage thickness decreased over time after surgery, and these defects were filled with MMP13- and VEGF-expressing fibrous tissue. The OARSI score increased over time in the middle region, and the score was significantly higher in the middle region than in the inner and outer regions at 1, 2, and 4 weeks after surgery. Col2-3/4c and MMP13 expression was observed primarily in the meniscus-covered outer region, in which the cartilage thickness increased over time. CONCLUSION: Loss of meniscal function caused cartilage degeneration and subchondral bone defects in the early phase site-specifically in the middle region. Furthermore, our results might indicate cartilage covered by menisci is easily degraded resulting in osmotic swelling of the cartilage in early OA.

Preventive effects of hyaluronan from deterioration of gait parameters in surgically induced mice osteoarthritic knee model.

OBJECTIVE: Osteoarthritis (OA) leads to pain and loss of function in affected joints. Gait disturbance results from these symptoms of OA, and gait analysis can be important to evaluate the progression of OA. The purpose of this study was to analyze gait pattern in a rodent model of OA and to assess the effects of intra-articular injection of hyaluronan (IAI-HA) by gait analysis, along with histological evaluation. DESIGN: OA was induced by destabilization of the medial meniscus (DMM) of C57BL/6 mice. IAI-HA started 3 weeks after DMM surgery. Mice were allocated to three groups and were given either 800-kDa HA (800-HA), 6000-kDa HA (6000-HA) or saline. We compared these three groups with a sham group by gait analysis using CatWalk. Histological evaluation was performed to assess articular cartilage changes in the knee joints. RESULTS: Mice injected with 800-HA or 6000-HA showed gait patterns similar to that of the sham mice, while the saline-injected group showed gait disturbances 12 and 16 weeks after DMM surgery. Histological changes in articular cartilage were similar among the 800-HA, 6000-HA and saline-treated groups, demonstrating OA progression throughout the experimental time points. Positive gait-related effects of IAI-HA might occur by its pain relieving effect and/or by preventing contracture. CONCLUSION: IAI-HA prevented gait disturbances in the DMM model, but did not prevent histological changes associated with OA progression.