Developmental process of the modern house shrew's molars: implications for the evolution of the tribosphenic molar in Mesozoic mammals.

Phylogenetically, the tribosphenic molars-prototypes of multi-cusped cheek teeth in marsupial and placental mammals-are derived from the single-cusped conical teeth of reptiles through the addition of cusps. Ontogenetically, mammalian molars are formed through the interface between the dental epithelium and mesenchyme (future enamel-dentin junction), becoming geometrically complex by adding epithelial signaling centers, called enamel knots, which determine future cusp positions. To reevaluate cusp homologies in Mesozoic mammals from an ontogenetic perspective, this study tracked molar development in a living placental mammal species, the house shrew (Suncus murinus), whose molars are morphologically the least derived from tribosphenic prototypes. The development of shrew molars proceeded as if it replayed the evolutionary process of tribosphenic molars. The first formed enamel knots gave rise to the evolutionarily oldest cusps-upper paracone and lower protoconid. The order of formation of other enamel knots and their location in development seemed to trace the order of cusp appearance in evolution. The parallel relationship between ontogeny and phylogeny of mammalian molars, if any, suggests that a change in the timing between developmental events rather than a change in the morphogenetic mechanism itself, should have been a major causal factor for the evolutionary transformation of tooth morphology.

Distinct Inflammatory Macrophage Populations Sequentially Infiltrate Bone-to-Tendon Interface Tissue After Anterior Cruciate Ligament (ACL) Reconstruction Surgery in Mice.

Macrophages are important for repair of injured tissues, but their role in healing after surgical repair of musculoskeletal tissues is not well understood. We used single-cell RNA sequencing (RNA-seq), flow cytometry, and transcriptomics to characterize functional phenotypes of macrophages in a mouse anterior cruciate ligament reconstruction (ACLR) model that involves bone injury followed by a healing phase of bone and fibrovascular interface tissue formation that results in bone-to-tendon attachment. We identified a novel "surgery-induced" highly inflammatory CD9+ IL1+ macrophage population that expresses neutrophil-related genes, peaks 1 day after surgery, and slowly resolves while transitioning to a more homeostatic phenotype. In contrast, CX3CR1+ CCR2+ macrophages accumulated more slowly and unexpectedly expressed an interferon signature, which can suppress bone formation. Deletion of Ccr2 resulted in an increased amount of bone in the surgical bone tunnel at the tendon interface, suggestive of improved healing. The "surgery-induced macrophages" identify a new cell type in the early phase of inflammation related to bone injury, which in other tissues is dominated by blood-derived neutrophils. The complex patterns of macrophage and inflammatory pathway activation after ACLR set the stage for developing therapeutic strategies to target specific cell populations and inflammatory pathways to improve surgical outcomes. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Stripe and spot selection in cusp patterning of mammalian molar formation.

Tooth development is governed largely by epithelial-mesenchymal interactions and is mediated by numerous signaling pathways. This type of morphogenetic processes has been explained by reaction-diffusion systems, especially in the framework of a Turing model. Here we focus on morphological and developmental differences between upper and lower molars in mice by modeling 2D pattern formation in a Turing system. Stripe vs. spot patterns are the primary types of variation in a Turing model. We show that the complexity of the cusp cross-sections can distinguish between stripe vs. spot patterns, and mice have stripe-like upper and spot-like lower molar morphologies. Additionally, our computational modeling that incorporates empirical data on tooth germ growth traces the order of cusp formation and relative position of the cusps in upper and lower molars in mice. We further propose a hypothetical framework of developmental mechanism that could help us understand the evolution of the highly variable nature of mammalian molars associated with the acquisition of the hypocone and the increase of lophedness.

Ptch2 is a Potential Regulator of Mesenchymal Stem Cells.

Ptch receptors 1 and 2 mediate Hedgehog signaling pivotal for organ development and homeostasis. In contrast to embryonic lethal Ptch1 -/- phenotype, Ptch2 -/- mice display no effect on gross phenotype. In this brief report, we provide evidence of changes in the putative incisor mesenchymal stem cell (MSC) niches that contribute to accelerated incisor growth, as well as intriguing changes in the bones and skin which suggest a role for Ptch2 in the regulation of MSCs and their regenerative potential. We employed histological, immunostaining, and computed tomography (µCT) analyses to analyze morphological differences between Ptch2 -/- and wild-type incisors, long bones, and skins. In vitro CFU and differentiation assays were used to demonstrate the MSC content and differentiation potential of Ptch2 -/- bone marrow stromal cells. Wound healing assay was performed in vivo and in vitro on 8-week-old mice to assess the effect of Ptch2 on the wound closure. Loss of Ptch2 causes increases in the number of putative MSCs in the continuously growing incisor, associated with increased vascularization observed in the tooth mesenchyme and the neurovascular bundle. Increased length and volume of Ptch2 -/- bones is linked with the increased number and augmented in vitro differentiation potential of MSCs in the bone marrow. Dynamic changes in the Ptch2 -/- skin thickness relate to changes in the mesenchymal compartment and impact the wound closure potential. The effects of Ptch2 abrogation on the postnatal MSCs suggest a crucial role for Ptch2 in Hedgehog signaling regulation of the organ regenerative potential.

The biological significance of tooth identification based on developmental and evolutional viewpoints.

BACKGROUND: Tooth identification is important not only for anatomists and anthropologists but also for dental practitioners and dental students studying dental anatomy courses. This review paper provides an overview of the significance of tooth identification focusing on the morphological and developmental background. HIGHLIGHT: The process of tooth identification comprises five steps of distinction: (1) between deciduous and permanent teeth; (2) between tooth classes; (3) between maxillary and mandibular teeth; (4) within the same tooth class; and (5) between the left and right sides of a tooth. According to Mühlreiter's features, the mesial half is more developed than the distal half, and the curvature feature is associated with the configuration of the dental arch. Each step of tooth identification refers to effective traits and characteristics. The possibility that systemic conditions affect dental morphology should be considered. Tooth identification is occasionally difficult owing to individual variations (size and shape, supernumerary tubercles, root fusion) and sex-based differences. A tooth type error within the same class is the most frequent error in tooth identification, followed by a left or right side error. CONCLUSION: To understand tooth identification, it is necessary to have comprehensive knowledge of dental morphology. A broad education with regard to tooth evolution and comparative odontology, as well as a thorough understanding of the morphology and function of teeth, which play a crucial role in sustaining life as organs of mastication, is essential.

Arthroscopic Bankart Repair and Open Bristow Procedure in the Treatment of Anterior Shoulder Instability With Osseous Glenoid Lesions in Collision Athletes.

BACKGROUND: Traumatic anterior shoulder instability in collision sports athletes often involves osseous glenoid lesions, which make surgical treatment challenging. High redislocation rates have been seen in collision sports athletes treated using arthroscopic Bankart repair. PURPOSE: To investigate the effectiveness of a combined arthroscopic Bankart repair and open Bristow procedure for the treatment of traumatic anterior shoulder instability in collision sports athletes, with a focus on osseous glenoid lesions. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We reviewed 149 shoulders in 141 competitive collision sports athletes (mean ± standard deviation age, 20.1 ± 4.1 years; 8 bilateral cases) who underwent a combined arthroscopic Bankart repair and open Bristow procedure with minimum 2 years of follow-up. Osseous Bankart lesions were arthroscopically reduced and fixed using a coracoid graft. RESULTS: Clinical outcomes as indicated by mean Rowe score improved significantly from 50.0 preoperatively to 98.9 postoperatively (P < .001) at a median follow-up of 3.4 years (range, 2.5-7 years). There were 2 recurrent dislocations (1.3%), both of which had nonunion of the transferred coracoid. Osseous Bankart lesions were observed in 85 shoulders, and osseous glenoid lesions ≥10% of the diameter of the nonoperative side were found in 58 shoulders, including 24 off-track cases. Clinical outcomes were not significantly different between patients with a glenoid defect ≥10% and <10%. Nonunion of the transferred coracoid was observed in 16 shoulders (10.7%), which had inferior Rowe scores; however, we could not define any risk factors for nonunion, including patient characteristics or bone morphology. Postoperative computed tomography performed in 29 patients >1 year after surgery showed successful repair of the osseous glenoid lesions, with a restored glenoid articular surface in all cases. Significant pre- to postoperative increases were seen in glenoid diameter (mean, 13.1% [95% CI, 9.9%-16.3%]; P < .001) and area (mean, 10.6% [95% CI, 8.5%-12.7%]; P < .001). CONCLUSION: A combined arthroscopic Bankart repair and open Bristow procedure improved bone morphology and was a reliable surgical method for treating collision sports athletes with traumatic anterior shoulder instability involving osseous glenoid lesions.

Comparison of Cellular Responses to TGF-ß1 and BMP-2 Between Healthy and Torn Tendons.

BACKGROUND: Tendons heal by fibrotic repair, increasing the likelihood of reinjury. Animal tendon injury and overuse models have identified transforming growth factor beta (TGF-ß) and bone morphogenetic proteins (BMPs) as growth factors actively involved in the development of fibrosis, by mediating extracellular matrix synthesis and cell differentiation. PURPOSE: To understand how TGF-ß and BMPs contribute to fibrotic processes using tendon-derived cells isolated from healthy and diseased human tendons. STUDY DESIGN: Controlled laboratory study. METHODS: Tendon-derived cells were isolated from patients with a chronic rotator cuff tendon tear (large to massive, diseased) and healthy hamstring tendons of patients undergoing anterior cruciate ligament repair. Isolated cells were incubated with TGF-ß1 (10 ng/mL) or BMP-2 (100 ng/mL) for 3 days. Gene expression was measured by real-time quantitative polymerase chain reaction. Cell signaling pathway activation was determined by Western blotting. RESULTS: TGF-ß1 treatment induced ACAN mRNA expression in both cell types but less in the diseased compared with healthy cells (P < .05). BMP-2 treatment induced BGN mRNA expression in healthy but not diseased cells (P < .01). In the diseased cells, TGF-ß1 treatment induced increased ACTA2 mRNA expression (P < .01) and increased small mothers against decapentaplegic (SMAD) signaling (P < .05) compared with those of healthy cells. Moreover, BMP-2 treatment induced ACTA2 mRNA expression in the diseased cells only (P < .05). CONCLUSION: Diseased tendon-derived cells show reduced expression of the proteoglycans aggrecan and biglycan in response to TGF-ß1 and BMP-2 treatments. These same treatments induced enhanced fibrotic differentiation and canonical SMAD cell signaling in diseased compared with healthy cells. CLINICAL RELEVANCE: Findings from this study suggest that diseased tendon-derived cells respond differently than healthy cells in the presence of TGF-ß1 and BMP-2. The altered responses of diseased cells may influence fibrotic repair processes during tendon healing.

Identifying Subjective Symptoms Associated with Psychomotor Disturbance in Melancholia: A Multiple Regression Analysis Study.

PURPOSE: Melancholia has recently been re-evaluated, because patients with major depressive disorder (MDD) were found to be heterogeneous. However, the DSM-5 criteria for melancholia (DSM-MEL) have been criticized, because of the difficulty in clearly distinguishing between melancholic and non-melancholic depression using DSM-MEL. Psychomotor disturbance (PMD) is one of the most important, as well as one of the only measurable symptoms of melancholia. Parker et al developed the CORE measure, which assesses PMD as a behavioral characteristic. The aim of our study was to objectively identify the subjective symptoms of melancholia by analyzing the symptoms associated with PMD. PATIENTS AND METHODS: A total of 106 participants with MDD were examined by psychiatrists. Multiple regression analysis was performed in which the total CORE score was the dependent variable, and items of the DSM-MEL and historically suggested melancholic features were independent variables. RESULTS: The following five independent variables were able to predict the total CORE score: 1) feelings of having lost feeling, 2) depressive delusions, 3) perplexity, 4) indecisiveness, and 5) no aggression against others. These five variables were more strongly associated with the total CORE score than the DSM-MEL. LIMITATION: The major limitation of this study was that when choosing non-DSM melancholic signs and symptoms, we did not comprehensively evaluate and select the symptoms but chose items that are clinically important. CONCLUSION: We identified five subjective symptoms that were associated with PMD. These five symptoms may be clinically useful as diagnostic criteria for melancholia.

Mapping molar shapes on signaling pathways.

A major challenge in evolutionary developmental biology is to understand how genetic mutations underlie phenotypic changes. In principle, selective pressures on the phenotype screen the gene pool of the population. Teeth are an excellent model for understanding evolutionary changes in the genotype-phenotype relationship since they exist throughout vertebrates. Genetically modified mice (mutants) with abnormalities in teeth have been used to explore tooth development. The relationship between signaling pathways and molar shape, however, remains elusive due to the high intrinsic complexity of tooth crowns. This hampers our understanding of the extent to which developmental factors explored in mutants explain developmental and phenotypic variation in natural species that represent the consequence of natural selection. Here we combine a novel morphometric method with two kinds of data mining techniques to extract data sets from the three-dimensional surface models of lower first molars: i) machine learning to maximize classification accuracy of 22 mutants, and ii) phylogenetic signal for 31 Murinae species. Major shape variation among mutants is explained by the number of cusps and cusp distribution on a tooth crown. The distribution of mutant mice in morphospace suggests a nonlinear relationship between the signaling pathways and molar shape variation. Comparative analysis of mutants and wild murines reveals that mutant variation overlaps naturally occurring diversity, including more ancestral and derived morphologies. However, taxa with transverse lophs are not fully covered by mutant variation, suggesting experimentally unexplored developmental factors in the evolutionary radiation of Murines.

The relationship between high-signal intensity changes in the glenohumeral joint capsule on MRI and clinical shoulder symptoms.

BACKGROUND/OBJECTIVE: High-signal intensity changes in the glenohumeral joint capsule on T2-and proton density-weighted magnetic resonance imaging are known as characteristic finding that is often observed in patients with frozen shoulder. We investigated the associations between high-signal intensity changes in the joint capsule on magnetic resonance imaging and the presence of rotator cuff tears and shoulder symptoms in patients with shoulder pain. METHODS: The medical records of 230 patients with shoulder pain who underwent magnetic resonance imaging at our hospital were reviewed. Patients were divided into three groups according to the presence and/or degree of rotator cuff tears (none, partial, or complete). The frequency of high-signal intensity changes in the joint capsule and its relationship with shoulder symptoms and the severity of rotator cuff tears were assessed. By quantitatively evaluating the intensity on MRI, the ratio between the joint capsule and the long head of the biceps (HSIC ratio) was calculated and compared with 15 healthy subjects. RESULTS: High-signal intensity changes were diagnosed in 165 (72%) patients, and it was significantly associated with night pain and range of motion limitation (p < 0.01). High-signal intensity changes were present in 66 patients (70%) with no rotator cuff tears, in 69 (71%) with partial rotator cuff tears, and in 36 (80%) with complete rotator cuff tears, without differences in their occurrence (p = 0.60), but were significantly associated with night pain in all the groups (p < 0.01) without differences in tear severity (p = 0.63). The ratio in the high-signal intensity changes (HSIC) positive group was approximately six times higher than that in the HSIC-negative and control groups (P < 0.01). Multivariate logistic regression analysis revealed that night pain is significantly associated with high-signal intensity changes (p < 0.01). CONCLUSION: Shoulder pain is a common and reliable clinical finding in patients with high-signal intensity changes, regardless of the presence and/or degree of rotator cuff tears, Such changes may indicate night pain and range of motion limitation in patients.

Metameric variation of upper molars in hominoids and its implications for the diversification of molar morphogenesis.

Metameric variation of molar size is in part associated with the dietary adaptations of mammals and results from slight alterations of developmental processes. Humans and great apes exhibit conspicuous variation in tooth morphology both between taxa and across tooth types. However, the manner in which metameric variation in molars emerged among apes and humans via evolutionary alterations in developmental processes remains largely unknown. In this study, we compare the enamel-dentine junction of the upper molars of humans-which closely correlates with morphology of the outer enamel surface and is less affected by wear-with that of the other extant hominoids: chimpanzees, bonobos, gorillas, orangutans, and gibbons. We used the morphometric mapping method to quantify and visualize three-dimensional morphological variation, and applied multivariate statistical analyses. Results revealed the following: 1) extant hominoids other than humans share a common pattern of metameric variation characterized by a largely linear change in morphospace; this indicates a relatively simple graded change in metameric molar shape; 2) intertaxon morphological differences become less distinct from the mesial to distal molars; and 3) humans diverge from the extant ape pattern in exhibiting a distinct metameric shape change trajectory in the morphospace. The graded shape change and lower intertaxon resolution from the mesial to distal molars are consistent with the concept of a 'key' tooth. The common metameric pattern observed among the extant nonhuman hominoids indicates that developmental patterns underlying metameric variation were largely conserved during ape evolution. Furthermore, the human-specific metameric pattern suggests considerable developmental modifications in the human lineage.

ERK1/2 drives IL-1ß-induced expression of TGF-ß1 and BMP-2 in torn tendons.

Diseased and injured tendons develop fibrosis, driven by factors including TGF-ß, BMPs and CTGF. IL-1ß and its signal transducer Erk1/2 are known to regulate TGF-ß expression in animal tendons. We utilised tissues and cells isolated from patients with shoulder tendon tears and tendons of healthy volunteers to advance understanding of how inflammation induces fibrosis in diseased human tendons. ERK1/2 expression was reduced in torn (diseased) compared to healthy patient tendon tissues. We next investigated the fibrotic responses of tendon-derived cells isolated from healthy and diseased human tendon tissues in an inflammatory milieu. IL-1ß treatment induced profound ERK1/2 signalling, TGFB1 and BMP2 mRNA expression in diseased compared to healthy tendon-derived cells. In the diseased cells, the ERK1/2 inhibitor (PD98059) completely blocked the IL-1ß-induced TGFB1 and partially reduced BMP2 mRNA expression. Conversely, the same treatment of healthy cells did not modulate IL-1ß-induced TGFB1 or BMP2 mRNA expression. ERK1/2 inhibition did not attenuate IL-1ß-induced CTGF mRNA expression in healthy or diseased tendon cells. These findings highlight differences between ERK1/2 signalling pathway activation and expression of TGF-ß1 and BMP-2 between healthy and diseased tendon tissues and cells, advancing understanding of inflammation induced fibrosis during the development of human tendon disease and subsequent repair.

Post-operative pain control following arthroscopic rotator cuff repair: peri-articular injection versus interscalene brachial plexus block.

PURPOSE: To compare post-operative pain relief with peri-articular injection (PI) versus interscalene brachial plexus block (IBPB) after arthroscopic rotator cuff repair (ARCR) surgery. METHODS: We retrospectively reviewed 121 consecutive patients undergoing ARCR surgery divided into two groups: the PI group and the IBPB group. We compared complications and self-reported pain score measured using a Numerical Rating Scale (NRS) during the initial 24 hours after surgery. RESULTS: The NRS scores recorded in the recovery room (0), 0.5, and four hours post-operatively were higher in the PI group (n = 38) than the IBPB group (n = 52) (2.1 vs. 0.8, p = 0.014; 1.4 vs. 0.5, p = 0.0069; and 1.3 vs. 0.5, p = 0.012, respectively). However, the NRS scores recorded at 16, 20, and 24 hours post-operatively were lower in the PI group than in the IBPB group (1.4 vs. 3.1, p < 0.0001; 1.4 vs. 3.2, p < 0.0001; and 1.7 vs. 3.2, p = 0.00046, respectively). The incidences of post-operative nausea and temporary numbness in the upper arm were significantly lower in the PI group than in the IBPB group (7.9% vs. 33%, p = 0.0052; and 13% vs. 85%, p < 0.0001, respectively). CONCLUSIONS: Although IBPB provided superior pain control during the initial few hours after ARCR surgery, PI was superior from 16 to 24 hours post-operatively. The rates of side effects, such as nausea and temporary arm numbness, were also lower in the PI group than in the IBPB group.

Craniofacial abnormality with skeletal dysplasia in mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase-1.

Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and plays an important part in organogenesis. To elucidate the roles of CS for craniofacial development, we analyzed the craniofacial morphology in CS N-acetylgalactosaminyltransferase-1 (T1) gene knockout (KO) mice. T1KO mice showed the impaired intramembranous ossification in the skull, and the final skull shape of adult mice included a shorter face, higher and broader calvaria. Some of T1KO mice exhibited severe facial developmental defect, such as eye defects and cleft lip and palate, causing embryonic lethality. At the postnatal stages, T1KO mice with severely reduced CS amounts showed malocclusion, general skeletal dysplasia and skin hyperextension, closely resembling Ehlers-Danlos syndrome-like connective tissue disorders. The production of collagen type 1 was significantly downregulated in T1KO mice, and the deposition of CS-binding molecules, Wnt3a, was decreased with CS in extracellular matrices. The collagen fibers were irregular and aggregated, and connective tissues were dysorganized in the skin and calvaria of T1KO mice. These results suggest that CS regulates the shape of the craniofacial skeleton by modulating connective tissue organization and that the remarkable reduction of CS induces hypoplasia of intramembranous ossification and cartilage anomaly, resulting in skeletal dysplasia.

Maternal undernutrition during early pregnancy inhibits postnatal growth of the tibia in the female offspring of rats by alteration of chondrogenesis.

Epidemiological research has suggested that birth weights are correlated with adult leg lengths. However, the relationship between prenatal undernutrition (UN) and postnatal leg growth remains controversial. We investigated the effects of UN during early pregnancy on postnatal hindlimb growth and determined whether early embryonic malnutrition affects the functions of postnatal chondrocytes in rats. Undernourished Wistar dams were fed 40% of the daily intake of rats in the control groups from gestational days 5.5-11.5, and femurs, tibias, and trunks or spinal columns were morphologically measured at birth and at 16 weeks of age in control and undernourished offspring of both sexes. We evaluated cell proliferation and differentiation of cultured chondrocytes derived from neonatal tibias of female offspring and determined chondrocyte-related gene expression levels in neonatal epiphysis and embryonic limb buds. Tibial lengths of undernourished female, but not male, offspring were longer at birth and shorter at 16 weeks of age (p < .05) compared with those of control rats. In chondrocyte culture studies, stimulating effects of IGF-1 on cell proliferation (p < .01) were significantly decreased and levels of type II collagen were lower in female undernourished offspring (p < .05). These phenomena were accompanied by decreased expression levels of Col2a1 and Igf1r and increased expression levels of Fgfr3 (p < .05), which might be attributable to the decreased expression of specificity protein 1 (p < .05), a key transactivator of Col2a1 and Igf1r. In conclusion, UN stress during early pregnancy reduces postnatal tibial growth in female offspring by altering the function of chondrocytes, likely reflecting altered expression of gene transactivators.

Intra- and inter-observer reproducibility of shoulder laxity tests: Comparison of the drawer, modified drawer and load and shift tests.

BACKGROUND: Conventional tests of shoulder laxity have been shown to have poor reliability due to the difficulty in palpating the subtle movements of the shoulder joint beneath the musculature. Modified drawer test that is performed while the soft tissues surrounding the shoulder are loosened has been proposed to facilitate glenohumeral joint movement and improve reliability. We hypothesised that the modified drawer test would have an improved intra- and inter-observer reproducibility in comparison to the drawer and load and shift tests. Correlation of shoulder laxity measured by these tests with generalized joint laxity was also assessed. METHODS: Forty healthy volunteers underwent bilateral shoulder examination in the clinic using the three tests for anterior and posterior laxity assessment by a consultant shoulder surgeon and a resident. The examination was repeated three months later by the same examiners in the same cohort. Intra- and inter- observer reproducibility was calculated using Kappa values. The correlation of shoulder with generalized joint laxity was also investigated. RESULTS: The modified drawer test showed significantly improved intra-observer reproducibility compared to the drawer test, but not to the load and shift (κ = 0.173, -0.042, and 0.009, respectively). There were no significant differences in the inter-observer reproducibility between the three tests (κ = 0.054, 0.055, and 0.056, respectively). Moderate correlation was noted between shoulder and generalized joint laxity when modified drawer test was used (r = 0.417). CONCLUSIONS: The modified drawer test improves intra- but not inter- observer reproducibility compared to the drawer test. Shoulder laxity assessed by the modified test correlated to generalized joint laxity. The modified drawer test has an improved reproducibility and correlation to generalized joint laxity over the conventional tests.

MRI for the diagnosis of scapular dyskinesis: a report of two cases.

Scapular dyskinesis describes the altered position of the scapula and/or abnormal movements of the scapulothoracic joint. It is caused by bony anatomical variations, bursitis, tumors, and muscular pathological conditions including loss of innervation and fibrosis. Scapular dyskinesis is just as often subclinical as it is symptomatic, and as the periscapular anatomical changes may not result in patient symptoms, a precise diagnosis of the etiology and pathophysiology has been a challenge. Scapular bony prominence is a common etiology of scapular dyskinesis, but does not always result in morbidity. We report a case of a 39-year-old man in whom an extensive MRI with fluid-sensitive imaging sequences covering the whole of the scapula was beneficial in diagnosing the inflammation adjacent to the bony deformity, which confirmed the etiology of scapular dyskinesis. Furthermore, in a 41-year old man without any anatomical variances, a similar MRI showed inflammation at the subscapular fossa that suggested altered scapular kinematics. An arthroscopic debridement of the lesion improved the symptoms. MRI in conjunction with plain radiographs, CT and physical examination enabled a precise diagnosis of the etiology. Fluid-sensitive MR images are important in defining the presence of inflammation, and are beneficial in determining the pathological significance of findings through other diagnostic measures.

Profibrotic mediators in tendon disease: a systematic review.

BACKGROUND: Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-ß), bone morphogenic proteins (BMPs) and connective tissue growth factor (CTGF) are key mediators in the pathogenesis of fibrotic disorders. The aim of this systematic review was to investigate the evidence for the expression of TGF-ß, BMPs and CTGF along tendon disease progression and the response of tendon cells to these growth factors accordingly. METHOD: We conducted a systematic screen of the scientific literature using the Medline database. The search terms used were "tendon AND TGF-ß," "tendon AND BMP" or "tendon AND CTGF." Studies of human samples, animal tendon injury and overuse models were included. RESULTS: Thirty-three studies were included. In eight studies the expression of TGF-ß, BMPs or CTGF was dysregulated in chronic tendinopathy and tendon tear patient tissues in comparison with healthy control tissues. The expression of TGF-ß, BMPs and CTGF was increased and showed temporal changes in expression in tendon tissues from animal injury or overuse models compared with the healthy control (23 studies), but the pattern of upregulation was inconsistent between growth factors and also the type of animal model. No study investigated the differences in the effect of TGF-ß, BMPs or CTGF treatment between patient-derived cells from healthy and diseased tendon tissues. Tendon cells derived from animal models of tendon injury showed increased expression of extracellular matrix protein genes and increased cell signaling response to TGF-ß and BMP treatments compared with the control cells (two studies). CONCLUSION: The expression of TGF-ß, BMPs and CTGF in tendon tissues is altered temporally during healing in animal models of tendon injury or overuse, but the transition during the development of human tendon disease is currently unknown. Findings from this systematic review suggest a potential and compelling role for TGF-ß, BMPs and CTGF in tendon disease; however, there is a paucity of studies analyzing their expression and stimulated cellular response in well-phenotyped human samples. Future work should investigate the dynamic expression of these fibrotic growth factors and their interaction with tendon cells using patient samples at different stages of human tendon disease.

Exploring metameric variation in human molars: a morphological study using morphometric mapping.

Human molars exhibit a type of metameric variation, which is the difference in serially repeated morphology within an organism. Various theories have been proposed to explain how this variation is brought about in the molars. Actualistic data that support the theories, however, are still relatively scarce because of methodological limitations. Here we propose new methods to analyse detailed tooth crown morphologies. We applied morphometric mapping to the enamel-dentine junction of human maxillary molars and examined whether odontogenetic models were adaptable to human maxillary molars. Our results showed that the upper first molar is phenotypically distinct among the maxillary molars. The average shape of the upper first molar is characterized by four well-defined cusps and precipitous surface relief of the occlusal table. On the other hand, upper third molar is characterized by smooth surface relief of the occlusal table and shows greater shape variation and distinct distribution patterns in morphospace. The upper second molar represents an intermediate state between first and third molar. Size-related shape variation was investigated by the allometric vector analysis, and it appeared that human maxillary molars tend to converge toward the shape of the upper first molar as the size increases. Differences between the upper first molar and the upper second and third molar can thus be largely explained as an effect of allometry. Collectively, these results indicate that the observed pattern of metameric variation in human molars is consistent with odontogenetic models of molar row structure (inhibitory cascade model) and molar crown morphology (patterning cascade model). This study shows that morphometric mapping is a useful tool to visualize and quantify the morphological features of teeth, which can provide the basis for a better understanding of tooth evolution linking morphology and development.

The Relationships of the Maxillary Sinus With the Superior Alveolar Nerves and Vessels as Demonstrated by Cone-Beam CT Combined With µ-CT and Histological Analyses.

There are no available detailed data on the three-dimensional courses of the human superior alveolar nerves and vessels. This study aimed to clarify the relationships of the maxillary sinus with the superior alveolar nerves and vessels using cone-beam computed tomography (CT) combined with µ-CT and histological analyses. Digital imaging and communication in medicine data obtained from the scanned heads/maxillae of cadavers used for undergraduate/postgraduate dissection practice and skulls using cone-beam CT were reconstructed into three-dimensional (3D) images using software. The 3D images were compared with µ-CT images and histological sections. Cone-beam CT clarified the relationships of the maxillary sinus with the superior alveolar canals/grooves. The main anterior superior alveolar canal/groove ran anteriorly through the upper part of the sinus and terminated at the bottom of the nasal cavity near the piriform aperture. The main middle alveolar canal ran downward from the upper part of the sinus to ultimately join the anterior one. The main posterior alveolar canal ran through the lateral lower part of the sinus and communicated with the anterior one. Histological analyses demonstrated the existence of nerves and vessels in these canals/grooves, and the quantities of these structures varied across each canal/groove. Furthermore, the superior dental nerve plexus exhibited a network that was located horizontally to the occlusal plane, although these nerve plexuses appeared to be the vertical network that is described in most textbooks. In conclusion, cone-beam CT is suggested to be a useful method for clarifying the superior alveolar canals/grooves including the nerves and vessels.