AIMS: Ossifying fibromyxoid tumour is a rare mesenchymal neoplasm predominantly affecting adults characterised by a multinodular growth pattern and the presence of a fibrous pseudocapsule with areas of ossification. Prompted by the recognition of a non-ossifying ossifying fibromyxoid tumour with lipomatous differentiation which caused diagnostic difficulty, we sought to further explore cases of ossifying fibromyxoid tumour with non-osseous heterologous elements. METHODS AND RESULTS: A search of our institutional and consultation archives revealed three additional cases that demonstrated lipomatous components and two cases with cartilaginous differentiation. RNA-sequencing revealed fusions involving PHF1 (n = 4) or EPC1 (n = 1) in all (five of five) cases tested, including EPC1::PHC1 and JAZF1::PHF1 fusions, which have not been reported before in ossifying fibromyxoid tumour. CONCLUSION: These six cases expand the histomorphological spectrum of ossifying fibromyxoid tumour, introducing lipomatous differentiation as a hitherto undocumented feature. Awareness of these rare variants will ensure appropriate diagnosis and clinical management.
- MeSH
- Cell Differentiation MeSH
- Cartilage pathology MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Lipoma * pathology diagnosis genetics MeSH
- Soft Tissue Neoplasms * pathology diagnosis genetics MeSH
- Fibroma, Ossifying * pathology diagnosis genetics MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Treatment of gingival fibroblasts with PDL extracellular vesicles results in promotion of Wnt signalling pathway and osteogenic differentiation. PDL secretome shows selective wound healing and matrix remodelling which can have implications for future periodontal regenerative strategies.
- MeSH
- Cell Differentiation MeSH
- Extracellular Vesicles * physiology MeSH
- Fibroblasts physiology MeSH
- Gingiva cytology MeSH
- Wound Healing physiology MeSH
- Humans MeSH
- Osteogenesis physiology MeSH
- Periodontal Ligament * cytology physiology MeSH
- Regeneration * physiology MeSH
- Wnt Signaling Pathway physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Východiska: Metastázy do kostí báze lební, vč. týlní kosti, jsou velmi vzácné. Tyto metastázy mohou vést k dysfunkci hypoglosálního nervu, což představuje diagnostický problém. Uvádíme případ karcinomu plic s dysfunkcí hypoglosálního nervu způsobenou metastázami do zadního kondylu týlní kosti. Případ: Dvaapadesátiletý muž byl odeslán do naší nemocnice kvůli dysfunkci hypoglosálního nervu a bolestem v týle. Zobrazovací techniky odhalily metastatickou lézi v zadním kondylu týlní kosti a 12mm uzlík v levém plicním hrotu. Histopatologické vyšetření potvrdilo adenokarcinom plic stadia IVB bez řídicích mutací nebo významné exprese PD-L1. Pacient podstoupil radioterapii zaměřenou na okcipitální lézi, po níž následovala systémová léčba karboplatinou, paklitaxelem, bevacizumabem a atezolizumabem. Udržovací léčba pokračovala podáváním bevacizumabu a atezolizumabu. Po 20 měsících sledování zůstal pacient bez onemocnění, přičemž dysfunkce hypoglosálního nervu vymizela. Zobrazovací techniky potvrdily osifikaci v místě kostní metastázy, což svědčí o příznivé odpovědi na léčbu. Závěr: Ačkoli jsou takové případy extrémně vzácné, tento článek poskytuje cenné informace o léčbě pacientů s podobnými metastázami. Včasná diagnóza a multidisciplinární přístup, zahrnující chemoterapii, imunoterapii a radioterapii, jsou nezbytné pro zlepšení výsledků u pacientů se vzácnými metastázami postihujícími zadní kondyl týlní kosti.
Background: A metastasis to the basilar bones, including the occipital bone, is extremely rare. Such metastases can result in hypoglossal nerve dysfunction, which poses diagnostic challenges. We report a case of lung cancer presenting with hypoglossal nerve dysfunction caused by metastasis to the posterior condyle of the occipital bone. Case: A 52-year-old man was referred to our hospital due to hypoglossal nerve dysfunction and occipital pain. Imaging studies revealed a metastatic lesion in the posterior condyle of the occipital bone and a 12- mm nodule in the apex of the left lung. Histopathological analysis confirmed stage IVB lung adenocarcinoma without actionable driver mutations or significant PD-L1 expression. The patient underwent radiation therapy targeting the occipital lesion, followed by systemic therapy with carboplatin, paclitaxel, bevacizumab, and atezolizumab. Maintenance therapy with bevacizumab and atezolizumab was continued. After 20 months of follow-up, the patient remained disease-free, with resolution of hypoglossal nerve dysfunction. Imaging confirmed ossification at the site of the bone metastasis, indicating a favorable response to treatment. Conclusion: Although such cases are extremely rare, this report provides valuable insight into the management of patients with similar metastases. Early diagnosis and a multidisciplinary approach, including chemotherapy, immunotherapy, and radiation therapy, are essential for improving outcomes in patients with rare metastases involving the posterior condyle of the occipital bone.
- Keywords
- syndrom okcipitálního kondylu,
- MeSH
- Adenocarcinoma of Lung * diagnostic imaging diagnosis drug therapy complications MeSH
- Diagnosis, Differential MeSH
- Drug Therapy classification methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Skull Base Neoplasms * diagnostic imaging diagnosis radiotherapy secondary MeSH
- Hypoglossal Nerve Diseases diagnosis etiology classification pathology MeSH
- Occipital Lobe pathology MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
Extracellular vesicles can play an important role in the processes occurring after stem cell transplantation, preventing cell apoptosis, stimulating immunological processes, and promoting the synthesis of extracellular matrix. Human follicular fluid (FF) can be a source of a subpopulation of cells with mesenchymal stem cells (MSCs) properties. Moreover these subpopulations of FF cells can differentiate into osteoblasts. In presented studies flow cytometry of ovarian FF cells confirmed positive expression of MSCs markers such as: CD44, CD90, CD105, CD73 and negative expression of a hematopoietic marker: CD45. The CD90+, CD105+, CD45- cell subpopulation has been obtained during magnetic separation using appropriate antibodies conjugated with microbeads. The extracellular vesicles (EVs) secreted by the cells during osteodifferentiation process differed from those secreted by cells culture in the basal medium. Based on the previous and current electron microscopy research, changes in size, number, and shape would support the notion that released EVs could be crucial to the ovarian FF cell subpopulation differentiation process. Osteogenic differentiation has been confirmed via Alizarin red staining. Therefore, follicular fluid (FF) can be a new source of a cell subpopulation with MSC properties, with the cells capable of differentiating into the osteogenic lineage. EVs could play a key role as mediators in tissue regeneration, especially bone tissue regeneration.
- MeSH
- Cell Differentiation * MeSH
- Extracellular Vesicles * ultrastructure metabolism MeSH
- Follicular Fluid * cytology metabolism MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mesenchymal Stem Cells * cytology metabolism MeSH
- Osteoblasts cytology metabolism MeSH
- Osteogenesis * MeSH
- Flow Cytometry MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The etiology of bone loss in celiac disease (CeD) remains a clinical challenge, with uncertainties present such as the extent of involvement of malabsorption and inflammation-induced osteoresorption processes in development of osteopenia/osteoporosis (OPN/OP), or reasons for failure to achieve healthy bone mass (BMD) even after long-term gluten-free diet (GFD) treatment. This observational prospective study explores the in vitro osteoclastogenic potential of peripheral blood precursors originating from adult active (newly diagnosed and untreated) celiac disease patients (aCeD) and describes the longitudinal changes in osteoclastogenesis after long-term adherence to GFD. To find connections between in vitro observations and in vivo bone metabolism changes, serum levels of 25(OH)D3, PTH, bCTX, PINP, CRP, IL-6, RANKL and OPG were measured before and after GFD and levels of these markers were correlated with the rate of osteoclastogenesis in vitro. OPG and IL-6 showed associations with BMD and/or presence of OPN/OP. Patients after GFD (CeD-GFD) exhibited improved BMD and increased serum 25(OH)D3 levels, alongside reduced bCTX and PINP levels. Compared to healthy donors, aCeD osteoclast genesis in vitro was higher and, surprisingly, remained elevated even in CeD-GFD patients. Negative correlation was found between osteoclastogenesis rate and serum OPG in aCeD, while osteoclastogenesis rate positively correlated with PTH in CeD-GFD. These results highlight OPG as marker for risk of OPN/OP in CeD and suggest that improvement of BMD after GFD is a result of uncoupling between bone metabolism and osteoresorptive action of osteoclasts after GFD.
- MeSH
- Diet, Gluten-Free * MeSH
- Celiac Disease * diet therapy metabolism MeSH
- Adult MeSH
- Interleukin-6 * blood metabolism MeSH
- Bone Density MeSH
- Middle Aged MeSH
- Humans MeSH
- Osteogenesis MeSH
- Osteoclasts metabolism MeSH
- Osteoporosis etiology metabolism MeSH
- Osteoprotegerin * blood metabolism MeSH
- Prospective Studies MeSH
- Vitamin D blood administration & dosage MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
OBJECTIVE: Insulin-sensitizing drugs, despite their broad use against type 2 diabetes, can adversely affect bone health, and the mechanisms underlying these side effects remain largely unclear. Here, we investigated the different metabolic effects of a series of thiazolidinediones, including rosiglitazone, pioglitazone, and the second-generation compound MSDC-0602K, on human mesenchymal stem cells (MSCs). METHODS: We developed 13C subcellular metabolomic tracer analysis measuring separate mitochondrial and cytosolic metabolite pools, lipidomic network-based isotopologue models, and bioorthogonal click chemistry, to demonstrate that MSDC-0602K differentially affected bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AT-MSCs). In BM-MSCs, MSDC-0602K promoted osteoblastic differentiation and suppressed adipogenesis. This effect was clearly distinct from that of the earlier drugs and that on AT-MSCs. RESULTS: Fluxomic data reveal unexpected differences between this drug's effect on MSCs and provide mechanistic insight into the pharmacologic inhibition of mitochondrial pyruvate carrier 1 (MPC). Our study demonstrates that MSDC-0602K retains the capacity to inhibit MPC, akin to rosiglitazone but unlike pioglitazone, enabling the utilization of alternative metabolic pathways. Notably, MSDC-0602K exhibits a limited lipogenic potential compared to both rosiglitazone and pioglitazone, each of which employs a distinct lipogenic strategy. CONCLUSIONS: These findings indicate that the new-generation drugs do not compromise bone structure, offering a safer alternative for treating insulin resistance. Moreover, these results highlight the ability of cell compartment-specific metabolite labeling by click reactions and tracer metabolomics analysis of complex lipids to discover molecular mechanisms within the intersection of carbohydrate and lipid metabolism.
- MeSH
- Adipogenesis * drug effects MeSH
- Cell Differentiation drug effects MeSH
- Hypoglycemic Agents pharmacology MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Metabolomics MeSH
- Mesenchymal Stem Cells * drug effects metabolism MeSH
- Osteogenesis * drug effects MeSH
- Pioglitazone pharmacology MeSH
- Rosiglitazone pharmacology MeSH
- Thiazolidinediones * pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The FGF signaling pathway plays an important role in the regulation of limb development, controlling cell migration, proliferation, differentiation, and apoptosis. Sprouty proteins act as antagonists of the FGF pathway and control the extent of FGF signaling as part of a negative feedback loop. Sprouty2/4 deficient mice evince defects in endochondral bone formation and digit patterning in their forelimbs, with pathogenesis recently related to ciliopathies. To understand the mechanisms behind these pathologies, the limb defects in Sprouty2+/-;Sprouty4-/- male and female mice were characterized and correlated to the dynamic expression patterns of Sprouty2 and Sprouty4, and the impact on the main signaling centers of the limb bud was assessed. Sprouty2 and Sprouty4 exhibited dynamic expressions during limb development. Interestingly, despite similar expression patterns in all limbs, the hindlimbs did not evince any obvious alterations in development, while the forelimbs showed consistent phenotypes of variable severity. Prenatally as well as postnatally, the left forelimb was significantly more severely affected than the right one. A broad variety of pathologies was present in the autopodium of the forelimb, including changes in digit number, size, shape, and number of bones, hand clefts, and digit fusions. Ectopic ossification of bones and abnormal bone fusions detected in micro-CT scans were frequently observed in the digital as well as in the carpal and metacarpal areas. Sprouty2+/-;Sprouty4-/- limb buds showed patchy loss of Fgf8 expression in the apical ectodermal ridge, and a loss of tissue underlying these regions. The zone of polarizing activity was also impacted, with lineage analysis highlighting a change in the contribution of Sonic hedgehog expressing cells. These findings support the link between Sproutys and Hedgehog signaling during limb development and highlight the importance of Sprouty2 and Sprouty4 in controlling early signaling centers in the limb.
- Publication type
- Journal Article MeSH
Bone lengthening and fracture repair depend on the anabolic properties of chondrocytes that function in an avascular milieu. The limited supply of oxygen and nutrients calls into question how biosynthesis and redox homeostasis are guaranteed. Here we show that glucose metabolism by the pentose phosphate pathway (PPP) is essential for endochondral ossification. Loss of glucose-6-phosphate dehydrogenase in chondrocytes does not affect cell proliferation because reversal of the non-oxidative PPP produces ribose-5-phosphate. However, the decreased NADPH production reduces glutathione recycling, resulting in decreased protection against the reactive oxygen species (ROS) produced during oxidative protein folding. The disturbed proteostasis activates the unfolded protein response and protein degradation. Moreover, the oxidative stress induces ferroptosis, which, together with altered matrix properties, results in a chondrodysplasia phenotype. Collectively, these data show that in hypoxia, the PPP is crucial to produce reducing power that confines ROS generated by oxidative protein folding and thereby controls proteostasis and prevents ferroptosis.
- MeSH
- Chondrocytes * metabolism MeSH
- Ferroptosis * physiology MeSH
- Glucosephosphate Dehydrogenase metabolism MeSH
- Glucose metabolism MeSH
- Mice MeSH
- Oxidation-Reduction MeSH
- Oxidative Stress * MeSH
- Pentose Phosphate Pathway * MeSH
- Reactive Oxygen Species * metabolism MeSH
- Protein Folding * MeSH
- Unfolded Protein Response MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: The primary aim of this study was to assess the amount and long-term stability of orthodontically created bone in patients with agenesis of maxillary lateral incisors after canine distalization. The secondary aim was to explore the impact of patient age on the process of alveolar bone resorption. METHODS: A group of patients with agenesis of the maxillary permanent lateral incisor was examined at 4 time points: the beginning of orthodontic treatment (T1, n = 80), the end of treatment (T2, n = 80), 2-5 years after treatment (T3, n = 79), and 12-15 years after treatment (T4, n = 32). The width of the edentulous alveolar bone was measured from study casts at the level of the bone ridge (point A) and 5 mm apically from the alveolar ridge (point B). Alveolar ridge height was also recorded using panoramic radiographs at all time points. Paired t tests, 2-sample t tests, Friedman test with Bonferroni correction, Spearman`s correlation, and linear regression tests were used to analyze the data. RESULTS: The alveolar ridge width was reduced by an average of 0.44 mm at point A and 0.47 mm at point B during the 12-15 years after treatment (T2-T4) and by 0.21 mm and 0.19 mm during the last 10 years (T3-T4). The alveolar ridge height was reduced by 0.59 mm between T2 and T4 and by 0.05 mm between T3 and T4. All reductions in ridge width and height were statistically significant (P <0.05). However, no significant correlation was observed between patient age and changes in alveolar bone parameters (P >0.05). CONCLUSIONS: Although the reductions in alveolar ridge dimensions were statistically significant, the orthodontically created bone after canine distalization remained stable 12-15 years after treatment in both the horizontal and vertical dimensions. Patient age did not significantly influence alveolar bone changes.
- MeSH
- Anodontia * therapy diagnostic imaging MeSH
- Jaw, Edentulous MeSH
- Child MeSH
- Adult MeSH
- Humans MeSH
- Maxilla * MeSH
- Adolescent MeSH
- Young Adult MeSH
- Follow-Up Studies MeSH
- Osteogenesis physiology MeSH
- Tooth Movement Techniques * methods MeSH
- Alveolar Process * diagnostic imaging pathology abnormalities MeSH
- Radiography, Panoramic MeSH
- Alveolar Bone Loss diagnostic imaging MeSH
- Incisor * abnormalities diagnostic imaging MeSH
- Age Factors MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
PURPOSE OF THE STUDY: Os vesalianum pedis (OVP) is a rare accessory bone of the foot located at the base of the fifth metatarsal bone. It is usually asymptomatic and incidentally seen on radiographs. When symptomatic, it manifests itself with lateral foot pain. OVP, which can become symptomatic as a result of traumatic injuries, can also be confused with fracture. The aim of this study is to determine the prevalence and morphometric characteristics of OVP in the Turkish population. MATERIAL AND METHODS: Radiographic images of 5268 individuals aged 16 years and older (mean 39.65±17.21) who completed ossification of the fifth metatarsal bone were evaluated for OVP. Of the cases included in the study, 44.8% were female and 55.2% were male. The general and sex-based prevalence of OVP was calculated, and morphometric measurements were done. RESULTS: OVP prevalence in the Turkish population was found to be 0.15% regardless of sex. OVP prevalence was calculated to be 0.24% in men and 0.04% in women. CONCLUSIONS: Anatomy, radiology, orthopedics and emergency medicine physicians are frequently encountered with foot disorders in clinical and educational practices. It is important to keep in mind the rare presence of OVP (0.15%), in the preliminary diagnosis. KEY WORDS: os vesalianum pedis, accessory ossicle, foot, radiography.
- MeSH
- Adult MeSH
- Clinical Relevance MeSH
- Middle Aged MeSH
- Humans MeSH
- Metatarsal Bones * diagnostic imaging abnormalities MeSH
- Adolescent MeSH
- Young Adult MeSH
- Prevalence MeSH
- Radiography methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Turkey MeSH
