Bone Sclerosis Research Articles

Genetic disruption of Ano5 leads to impaired osteoclastogenesis for gnathodiaphyseal dysplasia.

Gnathodiaphyseal dysplasia (GDD; OMIM#166260) is a rare skeletal genetic disorder characterized by sclerosis of tubular bones and cemento-osseous lesions in mandibles. TMEM16E/ANO5 gene mutations have been identified in patients with GDD. Here, Ano5 knockout (Ano5-/-) mice with enhanced osteoblastogenesis were used to investigate whether Ano5 disruption affects osteoclastogenesis. The maturation of osteoclasts, formation of F-actin ring and bone resorption were detected by immunohistochemistry, TRAP, phalloidin staining and Coming Osteo assays. The expression of osteoclast-related factors was measured by qRT-PCR. Early signaling pathways were verified by western blot. Ano5-/- mice exhibited inhibitory formation of multinucleated osteoclasts with a reduction of TRAP activity. The expression of Nfatc1, c-Fos, Trap, Ctsk, Mmp9, Rank and Dc-stamp was significantly decreased in bone tissues and bone marrow-derived macrophages (BMMs) of Ano5-/- mice. Ano5-/- osteoclasts manifested disrupted actin ring and less mineral resorption. RANKL-induced early signaling pathways were suppressed in Ano5-/- osteoclasts and Ano5 knockdown RAW264.7 cells. Moreover, the inhibitory effects of NF-κB signalling pathway on osteoclastogenesis were partially attenuated with NF-κB signalling activator. Ano5 deficiency impairs osteoclastogenesis, which leads to enhanced osteogenic phenotypes mediated by bone homeostasis dysregulation.

LncRNA HAGLR silencing inhibits IL-1β-induced chondrocytes inflammatory injury via miR-130a-3p/JAK1 axis

BackgroundOsteoarthritis (OA), the most common form of arthritis, is accompanied by destruction of articular cartilage, development of osteophyte and sclerosis of subchondral bone. This study aims to explore whether lncRNA HAGLR can play a role in OA, and further clarify the potential mechanism.Material and methodsStarBase and luciferase reporter assay were applied for predicting and confirming the interaction between lncRNA HAGLR, miR-130a-3p and JAK1. The levels of lncRNA HAGLR and miR-130a-3p were analyzed using quantitative reverse transcription PCR (qRT-PCR). The proliferation, cytotoxicity and apoptosis of CHON-001 cells were evaluated by MTT, lactate dehydrogenase assay (LDH) and Flow cytometry (FCM) analysis, respectively. Moreover, expression of cleaved Caspase3 protein were determined by Western blot assay. The release of inflammatory factors (TNF-α, IL-8, and IL-6) was detected by ELISA.ResultslncRNA HAGLR directly targets miR-130a-3p. Level of lncRNA HAGLR was substantially higher and miR-130a-3p level was memorably lower in IL-1β stimulated CHON-001 cells than that in Control group. Furthermore, lncRNA HAGLR silencing alleviated IL-1β induce chondrocyte inflammatory injury, as evidenced by increased cell viability, reduced LDH release, decreased apoptotic cells, inhibited cleaved-Caspase3 expression, and reduced secretion of secretion of inflammatory factors. However, miR-130a-3p-inhibitor reversed these findings. We also found miR-130a-3p directly targeted JAK1 and negatively regulated JAK1 expression in CHON-001 cells. In addition, JAK1-plasmid reversed the effects of miR-130a-3p mimic on IL-1β-induced chondrocytes inflammatory injury.ConclusionSilencing of lncRNA HAGLR alleviated IL-1β-stimulated CHON-001 cells injury through miR-130a-3p/JAK1 axis, revealing lncRNA HAGLR may be a valuable therapeutic target for OA therapy.

Salivary biglycan-neo-epitope-BGN262: A novel surrogate biomarker for equine osteoarthritic sub-chondral bone sclerosis and to monitor the effect of short-term training and surface arena

ObjectiveWe aimed to delineate a novel soluble Biglycan Neo-epitope-BGN262 in saliva from young reference and osteoarthritic horses in conjunction with the influence of short-term training exercise, riding surface hardness, circadian rhythm, and feeding on its soluble levels. DesignA custom-made inhibition ELISA was used for the quantification of BGN262 in saliva. Cohort 1: A cross-sectional study comprising reference (N ​= ​19) and OA horses (N ​= ​9) with radiographically classified subchondral bone sclerosis. Receiver operating characteristic curve analysis was performed to evaluate the robustness of BGN262. Cohorts 2 (N ​= ​5) & 3 (N ​= ​7): Longitudinal studies of sampling during a short-term training exercise (sand-fibre) and a cross-over design of short-training exercise on 2 different riding arenas (sand and sand-fibre), respectively. Capillary western immunoassay was used to determine the BGN262 molecular size in a selection of saliva samples collected from cohort 1. ResultsCohort 1: Salivary BGN262 levels were significantly higher in the OA group. The Receiver operating characteristic curve analysis showed an area under the curve of 0.8304 [0.6386 to 1.022], indicating a good separation from the reference group. Cohorts 2 & 3: Salivary BGN262 levels significantly changed during the exercise on sand and sand-fibre arena, with a trend towards higher levels for sand-fibre. The size of the BGN262 fragment determined by Capillary western assay was 18 ​kDa. ConclusionsThe data presented show saliva BGN262 levels as a novel biomarker in evaluating the influence of exercise, and interaction with riding arenas alongside assessing osteoarthritis severity.

Metformin Attenuates the Inflammatory Response via the Regulation of Synovial M1 Macrophage in Osteoarthritis

Osteoarthritis (OA), the most common chronic inflammatory joint disease, is characterized by progressive cartilage degeneration, subchondral bone sclerosis, synovitis, and osteophyte formation. Metformin, a hypoglycemic agent used in the treatment of type 2 diabetes, has been evidenced to have anti-inflammatory properties to treat OA. It hampers the M1 polarization of synovial sublining macrophages, which promotes synovitis and exacerbates OA, thus lessening cartilage loss. In this study, metformin prevented the pro-inflammatory cytokines secreted by M1 macrophages, suppressed the inflammatory response of chondrocytes cultured with conditional medium (CM) from M1 macrophages, and mitigated the migration of M1 macrophages induced by interleukin-1ß (IL-1ß)-treated chondrocytes in vitro. In the meantime, metformin reduced the invasion of M1 macrophages in synovial regions brought about by the destabilization of medial meniscus (DMM) surgery in mice, and alleviated cartilage degeneration. Mechanistically, metformin regulated PI3K/AKT and downstream pathways in M1 macrophages. Overall, we demonstrated the therapeutic potential of metformin targeting synovial M1 macrophages in OA.

The promising role of DECT in the diagnosis of Osteitis Condensans Ilii: a case report.

Osteitis condensans ilii (OCI) is a noninflammatory condition of no clear etiology, cause of axial low back pain. It is characterized by sclerotic bone lesions at the iliac region of the sacroiliac joints. The diagnosis is based on radiological findings and the exclusion of other conditions associated with back pain. We present a case of bilateral OCI in a young woman with bone sclerosis at sacroiliac joints diagnosed with the use of Dual Energy CT.

Erdheim-Chester disease with a late onset cardiovascular manifestations: A case report

Introduction: Erdheim-Chester disease (ECD) is an uncommon non Langerhans cell histiocytosis. Bilateral symmetric sclerosis of the long bones and probable multiorgan involvement are the main manifestations of this condition. Here, we report a case of ECD showing diffuse thickening of the aorta’s entire wall and pericardial effusion.

Intensive cholesterol-lowering treatment reduces synovial inflammation during early collagenase-induced osteoarthritis, but not pathology at end-stage disease in female dyslipidemic E3L.CETP mice

The association between metabolic syndrome (MetS) and osteoarthritis (OA) development has become increasingly recognized. In this context, the exact role of cholesterol and cholesterol-lowering therapies in OA development has remained elusive. Recently, we did not observe beneficial effects of intensive cholesterol-lowering treatments on spontaneous OA development in E3L.CETP mice. We postulated that in the presence of local inflammation caused by a joint lesion, cholesterol-lowering therapies may ameliorate OA pathology. Female ApoE3∗Leiden.CETP mice were fed a cholesterol-supplemented Western type diet. After 3 weeks, half of the mice received intensive cholesterol-lowering treatment consisting of atorvastatin and the anti-PCSK9 antibody alirocumab. Three weeks after the start of the treatment, OA was induced via intra-articular injections of collagenase. Serum levels of cholesterol and triglycerides were monitored throughout the study. Knee joints were analyzed for synovial inflammation, cartilage degeneration, subchondral bone sclerosis and ectopic bone formation using histology. Inflammatory cytokines were determined in serum and synovial washouts. Cholesterol-lowering treatment strongly reduced serum cholesterol and triglyceride levels. Mice receiving cholesterol-lowering treatment showed a significant reduction in synovial inflammation (P=0.008, WTD: 95% CI: 1.4- 2.3; WTD+AA: 95% CI: 0.8- 1.5) and synovial lining thickness (WTD: 95% CI: 3.0-4.6, WTD+AA: 95% CI: 2.1-3.2) during early-stage collagenase-induced OA. Serum levels of S100A8/A9, MCP-1 and KC were significantly reduced after cholesterol-lowering treatment (P=0.0005, 95% CI:-46.0 to-12.0; P=2.8×10-10, 95% CI:-398.3 to-152.1; P=2.1×10-9,-66.8 to-30.4, respectively). However, this reduction did not reduce OA pathology, determined by ectopic bone formation, subchondral bone sclerosis and cartilage damage at end-stage disease. This study shows that intensive cholesterol-lowering treatment reduces joint inflammation after induction of collagenase-induced OA, but this did not reduce end stage pathology in female mice.

Dental Pulp Stem Cell-Derived Exosomes Alleviate Mice Knee Osteoarthritis by Inhibiting TRPV4-Mediated Osteoclast Activation.

Osteoarthritis (OA) is a degenerative disease that causes chronic pain and joint swelling and even disables millions of patients. However, current non-surgical treatment for OA can only relieve pain without obvious cartilage and subchondral bone repair. Mesenchymal stem cell (MSC)-secreted exosomes have promising therapeutic effects on knee OA, but the efficacy of MSC-exosome therapy is not well determined, and the mechanisms involved are still unclear. In this study, we isolated dental pulp stem cell (DPSC)-derived exosomes by ultracentrifugation and determined the therapeutic effects of a single intra-articular injection of DPSC-derived exosomes in a mice knee OA model. The results showed that the DPSC-derived exosomes effectively improved abnormal subchondral bone remodeling, inhibited the occurrence of bone sclerosis and osteophytes, and alleviated cartilage degradation and synovial inflammation in vivo. Moreover, transient receptor potential vanilloid 4 (TRPV4) was activated during the progression of OA. Enhanced TRPV4 activation facilitated osteoclast differentiation, and TRPV4 inhibition blocked this process in vitro. DPSC-derived exosomes repressed osteoclast activation in vivo by inhibiting TRPV4 activation. Our findings demonstrated that a topical, single injection of DPSC-derived exosomes is a potential strategy for knee OA treatment, and that the exosomes regulated osteoclast activation by TRPV4 inhibition, which may act as a promising target for clinical OA treatment.

Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis

Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown. To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis. A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n= 46), (2) significant bone loss (n= 47), and (3) diffuse bone sclerosis (n= 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis. Bone loss was associated with significantly higher levels of serum baseline tryptase (P= .01), IFN-γ (P= .05), IL-1β (P= .05), and IL-6 (P= .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P< .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P= .01), together with lower IFN-γ (P= .03) and RANK-ligand (P= .04) plasma levels versus healthy bone cases. SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.

Treatment of osteoarthritis by salvianolic acid derivatives.

Osteoarthritis (OA) is a pervasive degenerative joint disorder. Approximately 32.5 million US adults are suffering from this disease. The joint disease is characterized by oxidative stress, synovial fluid inflammation, apoptosis in chondrocytes, cartilage degradation, bone sclerosis, and osteophyte formation. Reactive oxygen species (ROS) production due to oxidative stress is the primary cause of many pathological disease processes. The understanding of molecular and cellular pathways and their association with joint tissues is necessary to develop new therapeutic approaches for the prevention and treatment of OA. Most over-the-counter non-steroidal anti-inflammatory drugs are used to treat OA. Natural compounds with medicinal properties are useful and effective sources for the treatment of various diseases since ancient times. Salvianolic acid is one of the natural phenolic compounds of the plant Radix Salvia miltiorrhiza having antioxidant, anti-inflammatory, antimicrobial, anesthetic, and cytotoxic properties. There is a critical need for new drug planning to focus on the specific mechanisms of oxidative interaction in targeted TRPA1 ion channels and intracellular ion signaling, which will interact with other TRP channel subunits to regulate pathological diseases. In our experiment, we found that the rise of intracellular calcium ions in rat osteoblast cells due to excessive free radicals generated by H2O2 was suppressed by Salvianolic Acid-B. Therefore, this pilot project aims to identify Salvianolic acid analogs as lead compounds that target the TRP channel which is one of the key pathway players in producing arthritis pain and other pathogenesis.

Chondroprotective Mechanism of Eucommia ulmoides Oliv.-Glycyrrhiza uralensis Fisch. Couplet Medicines in Knee Osteoarthritis via Experimental Study and Network Pharmacology Analysis.

Knee osteoarthritis (KOA) is the primary prevalent disabling joint disorder among osteoarthritis (OA), and there is no particularly effective treatment at the clinic. Traditional Chinese medicine (TCM) herbs, such as Eucommia ulmoides Oliv. and Glycyrrhiza uralensis Fisch. (E.G.) couplet medicines, have been reported to exhibit beneficial health effects on KOA, exact mechanism of E.G. nevertheless is not fully elucidated. We assess the therapeutic effects of E.G. on KOA and explore its underlying molecular mechanism. UPLC-Q-TOF/MS technique was used to analyze the active chemical constituents of E.G. The destabilization of the medial meniscus model (DMM) was employed to evaluate the chondroprotective action of E.G. in KOA mice using histomorphometry, μCT, behavioral testing and immunohistochemical staining. Additionally, network pharmacology and molecular docking were used to predict potential targets for anti-KOA activities of E.G., which was further verified through in vitro experiments. In vivo studies have shown that E.G. could significantly ameliorate DMM-induced KOA phenotypes including subchondral bone sclerosis, cartilage degradation, gait abnormality and thermal pain reaction sensibility. E.G. treatment could also promote extracellular matrix synthesis to protect articular chondrocytes, which was indicated by Col2 and Aggrecan expressions, as well as reducing matrix degradation by inhibiting MMP13 expression. Interestingly, network pharmacologic analysis showed that PPARG might be a therapeutic center. Further study proved that E.G.-containing serum (EGS) could up-regulate PPARG mRNA level in IL-1β-induced chondrocytes. Notably, significant effects of EGS on the increment of anabolic gene expressions (Col2, Aggrecan) and the decrement of catabolic gene expressions (MMP13, Adamts5) in KOA chondrocytes were abolished due to the silence of PPARG. E.G. played a chondroprotective role in anti-KOA by inhibiting extracellular matrix degradation, which might be related to PPARG.

Integration of metabolomics and transcriptomics provides insights into enhanced osteogenesis in Ano5Cys360Tyr knock-in mouse model.

Gnathodiaphyseal dysplasia (GDD; OMIM#166260) is a rare autosomal dominant disorder characterized by diaphyseal sclerosis of tubular bones and cemento-osseous lesions in mandibles. GDD is caused by point mutations in the ANO5 gene. However, the mechanisms underlying GDD have not been disclosed. We previously generated the first knock-in mouse model for GDD expressing a human mutation (p.Cys360Tyr) in ANO5 and homozygous Ano5 knock-in (Ano5KI/KI ) mice exhibited representative traits of human GDD especially including enhanced osteogenesis. Metabolomics and transcriptomics analyses were conducted for wildtype (Ano5+/+ ) and Ano5KI/KI mature mouse calvarial osteoblasts (mCOBs) grown in osteogenic cultures for 14 days to identify differential intracellular metabolites and genes involved in GDD. Subsequently, related differential genes were validated by qRT-PCR. Cell proliferation was confirmed by CCK8 assay and calcium content in mineral nodules was detected using SEM-EDS. Metabolomics identified 42 differential metabolites that are primarily involved in amino acid and pyrimidine metabolism, and endocrine and other factor-regulated calcium reabsorption. Concomitantly, transcriptomic analysis revealed 407 differentially expressed genes in Ano5KI/KI osteoblasts compared with wildtype. Gene ontology and pathway analysis indicated that Ano5Cys360Tyr mutation considerably promoted cell cycle progression and perturbed calcium signaling pathway, which were confirmed by validated experiments. qRT-PCR and CCK-8 assays manifested that proliferation of Ano5KI/KI mCOBs was enhanced and the expression of cell cycle regulating genes (Mki67, Ccnb1, and Ccna2) was increased. In addition, SEM-EDS demonstrated that Ano5KI/KI mCOBs developed higher calcium contents in mineral nodules than Ano5+/+ mCOBs, while some calcium-related genes (Cacna1, Slc8a1, and Cyp27b1) were significantly up-regulated. Furthermore, osteocalcin which has been proved to be an osteoblast-derived metabolic hormone was upregulated in Ano5KI/KI osteoblast cultures. Our data demonstrated that the Ano5Cys360Tyr mutation could affect the metabolism of osteoblasts, leading to unwonted calcium homeostasis and cellular proliferation that can contribute to the underlying pathogenesis of GDD disorders.

Subchondral Bone Cyst Development in Osteoarthritis: From Pathophysiology to Bone Microarchitecture Changes and Clinical Implementations.

Osteoarthritis is a degenerative joint disease affecting middle-aged and elderly patients. It mainly involves weight-bearing joints such as the hip, knee and spine as well as the basilar joint of the thumb, causing dysfunction and painful symptoms. Often, joint arthritis is accompanied by cartilage defects, joint space narrowing, osteophytes, bone sclerosis and subchondral bone cysts (SBC). The aim of the present study was to explore the pathophysiology responsible for the development of SBCs as well as the association between SBCs and disease progress, the level of clinical symptoms and their impact on postoperative outcomes and risk of possible complications following joint replacements if left untreated. A literature review on PubMed articles was conducted to retrieve and evaluate all available evidence related to the main objective mentioned above. A few theories have been put forth to explain the formation process of SBCs. These involve MMPs secretion, angiogenesis, and enhanced bone turnover as a biological response to abnormal mechanical loads causing repeated injuries on cartilage and subchondral tissue during the development of arthritis. However, the application of novel therapeutics, celecoxib-coated microspheres, local administration of IGF-1 and activated chondrocytes following surgical debridement of SBCs hinders the expansion of SBCs and prevents the progression of osteoarthritis.

Prevalence of Frontotemporal Dementia in Females of 5 Hispanic Families With R159H VCP Multisystem Proteinopathy.

Missense variants of the valosin-containing protein (VCP) gene cause a progressive, autosomal dominant disease termed VCP multisystem proteinopathy (MSP1). The disease is a constellation of clinical features including inclusion body myopathy (IBM), Paget disease of bone (PDB), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), typically reported at a frequency of 90%, 42%, 30%, and 9%, respectively. The Hispanic population is currently underrepresented in previous reports of VCP myopathy. We expand our genotype-phenotype studies in 5 Hispanic families with the c.476G>A, p.R159H VCP variant. We report detailed clinical findings of 11 patients in 5 Hispanic families with the c.476G > A, p.R159H VCP variant. In addition, we report frequencies of the main manifestations in 28 additional affected members of the extended family members. We also compared our findings with an existing larger cohort of patients with VCP MSP1. FTD was the most prevalent feature reported, particularly frequent in females. PDB was only seen in 1 patient in contrast to the earlier reported cohorts. The overall frequency of the different manifestations: myopathy, PDB, FTD, and ALS in these 5 families was 39%, 3%, 72%, and 8%, respectively. The atypical phenotype and later onset of manifestations in these families resulted in a noticeable delay in the diagnosis of VCP disease. Studying each VCP variant in the context of ethnic backgrounds is pivotal in increasing awareness of the variability of VCP-related diseases across different ethnicities, enabling early diagnosis, and understanding the mechanism for these genotype-phenotype variations.

Targeting CD38 to Suppress Osteoarthritis Development and Associated Pain After Joint Injury in Mice.

This study was undertaken to determine the role of CD38, which can function as an enzyme to degrade NAD+ , in osteoarthritis (OA) development. Human knee cartilage from normal donors and OA donors were examined for CD38 expression. "Gain-of-function," through overexpression of CD38 via transient transfection, and "loss-of-function," through pharmacologic inhibition of CD38, approaches were used to assess the effects of CD38 on intracellular NAD+ :NADH ratio and catabolic activity in chondrocytes. We also initiated joint injury-induced OA by surgical destabilization of the medial meniscus (DMM) in CD38 knockout mice and wild-type (WT; C57BL/6) mice and in WT male mice in the presence or absence of apigenin treatment. Cartilage degradation, synovial inflammation, subchondral bone changes, and pain behavior were evaluated after DMM surgery. We also examined expression of CD38 and the neuropeptide calcitonin gene-related peptide (CGRP) in knee sections from these mice. CD38 expression was up-regulated in human knee OA cartilage and in chondrocytes stimulated with the proinflammatory cytokine interleukin-1β (IL-1β). Overexpression of CD38 in chondrocytes resulted in reduced cellular NAD+ :NADH ratio and augmented catabolic responses to IL-1β. These effects were reversed by pharmacologic inhibition of CD38. Cartilage degradation and synovial inflammation, associated with increased CD38 expression in cartilage and synovium, osteophyte formation and subchondral bone sclerosis, and pain-like behavior linked to increased CGRP expression in the synovium were observed in WT mice after joint injury. Such effects were significantly reduced in mice deficient in CD38 through either genetic knockout or pharmacologic inhibition. CD38 deficiency exerts OA disease-modifying effects. Inhibition of CD38 has the potential to be a novel therapeutic approach for OA treatment.

Diagnostic Accuracy of Computed Tomography by Fungal Sinusitis: A Case-control Study

Introduction: Recent decades show a considerable increase in fungal infections, hence can lead to fungal sinusitis. Immunosuppression, post organ transplant, diabetes mellitus, and Human Immunodeficiency Virus (HIV) infection have led to a rise in the incidence of fungal infections. Recent advances in nasal endoscopy, Computed Tomography (CT), and Histopathological Examination (HPE) Techniques have led to better detection of fungal aetiology. Aim: To determine the most significant CT findings in fungal sinusitis or combination of findings in comparison to HPE. Materials and Methods: This retrospective case-control study was done at Sri Manakula Vinayagar Medical College and Hospital, Puducherry from January 2017 to December 2020. Total number of patients were 90. Total 50 cases of fungal sinusitis confirmed with histopathological confirmation and available non contrast CT Paranasal Sinus (PNS) images where time interval between CT and Functional Endoscopic Sinus Surgery (FESS) not exceeding ten days were included. The control group had 40 patients with chronic sinusitis with HPE negative results. CT PNS were performed on PHILIPS 16 slice scanner without contrast administration. Data was entered into Microsoft excel and analysed using Statistical Package for the Social Sciences (SPSS) 22.0 version software. Results: Mean age of the cases (fungal sinusitis) were 46.7±17 years and 39±13.1 years of controls. Of the total 90 subjects, heterogeneous mucosal thickening was seen in 41 (45.6%), intrasinus hyperattenuation in 36 (40%), bone sclerosis in 44 (48.9%), bone erosion in 36 (40%), sinus expansion in 23 (25.6%) subjects. Fungal sinusitis patients had more proportion of these findings when compared to control group and hence p-value was significant. Conclusion: The CT diagnostic features of the fungal sinusitis are heterogeneous mucosal thickening, intrasinus hyperattenuation, bone sclerosis, bone erosion and sinus expansion which were significant. These findings help to differentiate fungal sinusitis from non fungal sinusitis.

Osteoarthritis: A contemporary view of the problem, the possibilities of therapy and prospects for further research

Osteoarthritis is a chronic degenerative disease characterized by the destructive changes in the articular cartilage, synovitis, subchondral bone sclerosis and osteophyte formation. Today it is the most common joint disease and one of the main causes of disability of elderly people.&lt;br /&gt; This review provides an overview of advances in understanding of osteoarthritis etiology, pathogenesis, histopathology, as well as the results of up-to-date research of the molecular mechanisms underlying this heterogeneous age-related disease at the clinical and fundamental levels.&lt;br /&gt; The article is devoted to a comprehensive review of the osteoarthritis problem, compiled considering the classical understanding of morphological changes, clinical picture, diagnostic methods, and current therapy protocols, supplemented by the modern trends of world research with the prospect of further development and implementation of the latest therapeutic methods, such as nerve growth factor-inhibitors, fibroblast growth factor-18 and stem cells treatments.

Effects of Immobilization and Swimming on the Progression of Osteoarthritis in Mice

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration of articular cartilage and thickening and sclerosis of the subchondral bone. Mechanical factors play significant roles in the development and progression of OA, but it is still controversial whether exercise or rest is a more effective treatment for OA patients. In this study, we compared the effects of swimming and immobilization at different stages of OA in mice. Four weeks (the middle stage of OA) or eight weeks (the late stage of OA) after DMM (destabilization of the medial meniscus) surgery, the mice were subjected to four-week immobilization or swimming. Ink blot analysis and a beam walking test were performed to measure the gait and balance ability. Histological analysis was performed to determine the trabecular bone area, the thickness of subchondral bone, the thickness of the cartilage, the OARSI score, and the expression of MMP13 (matrix metalloproteinases) and IL-6 (interleukin). The results showed that at the middle stage of OA, both immobilization and swimming slowed down the progression of OA. Immobilization relieved OA to a certain extent by decreasing the production of regulatory factors to attenuate the degeneration of cartilage, which partly relieved the effects of DMM on gait, mainly in the hindlimb. Swimming mainly attenuated the thickening and rescued the area of subchondral bone.

Clinical Evaluation of the Knee Arthritis Patient

The evaluation of a patient with knee osteoarthritis (OA) has 3 main components: clinical history, physical examination, and radiographic imaging. The clinician should assess for inciting and aggravating factors for the knee pain as well as for the presence of any mechanical symptoms. A history of prior knee injury or surgery can suggest the development of early osteoarthritis. A thorough physical examination of the knee should be performed. Some features of OA include limited range of motion, crepitus in the patellofemoral compartment, and joint line tenderness. Depending on the severity of OA varus or valgus alignment can develop. Special tests such as the McMurray for meniscal tears may cause increased pain as patients with OA will often have degenerative meniscal tears. Weight bearing radiographs can confirm the diagnosis of OA. Several scales exist to grade the severity of OA with the Kellgren-Lawrence being one that is often used. Radiographic features of OA include joint space narrowing, osteophytes, sclerosis of bone and bone end deformities. If after the above evaluation the diagnosis is still unclear, advanced imaging or laboratory testing can be performed to evaluate for alternative diagnoses.

Van Buchem disease: A rare sclerosing dysplasia

The other name for Van Buchem disease is hyperostosis corticalis generalisata. It is an uncommon genetic bone condition characterized by aberrant metaphyseal expansion of the tubular bones and hyperostosis and sclerosis of the craniofacial bones. It is brought on by a SOST gene defect that results in increased osteoblastic activity. A 20-year-old male patient came to us with gradual hearing loss, progressive facial deformity, and breathing difficulties. Radiological examination with computed tomography and X-ray reveals sclerosis of the craniofacial bones and enlargement of the metaphyseal region of long tubular bones. Based on radiological characteristics, we suspected it to be a very rare case of sclerosing dysplasia called Van Buchem disease.