Interleukin-6 signaling in osteoblasts regulates bone remodeling during exercise

Aerobic exercise has many beneficial effects on human health. One of them, is to influence positively bone remodeling through, however, incompletely understood mechanisms. Given its recently demonstrated role as a mediator of the bone to muscle to bone crosstalk during exercise, we hypothesized that interleukin-6 (IL-6) signaling in bone may contribute to the beneficial effect that exercise has on bone homeostasis. In this study, we first show that aerobic exercise increases the expression of Il6r in bones of WT mice. Then, we analyzed a mutant mouse strain that lacks the IL-6 receptor alpha specifically in osteoblasts (Il6rosb-/-). As it has been reported in the case of Il6-/- mice, in sedentary conditions, bone mass and remodeling were normal in adult Il6rosb-/- mice when compared to controls. In contrast, Il6rosb-/- mice that were subjected to aerobic exercise did not show the increase in bone mass and remodeling parameters that control littermates demonstrated. Moreover, Il6rosb-/- mice undergoing aerobic exercise showed a severe impairment in bone formation, indicating that activation of bone-forming cells is defective when IL-6 signaling in osteoblasts is disrupted. In sum, this study provides evidence that a function of IL-6 signaling in osteoblasts is to promote high bone turnover during aerobic exercise

Naso-Ethmoidal Phosphaturic Mesenchymal Tumor: A Rare Tumor Site for an Uncommon Paraneoplastic Syndrome

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Inflammatory Responses and Barrier Function of Endothelial Cells Derived from Human Induced Pluripotent Stem Cells

Several studies have reported endothelial cell (EC) derivation from human induced pluripotent stem cells (hiPSCs). However, few have explored their functional properties in depth with respect to line-to-line and batch-to-batch variability and how they relate to primary ECs. We therefore carried out accurate characterization of hiPSC-derived ECs (hiPSC-ECs) from multiple (non-integrating) hiPSC lines and compared them with primary ECs in various functional assays, which included barrier function using real-time impedance spectroscopy with an integrated assay of electric wound healing, endothelia-leukocyte interaction under physiological flow to mimic inflammation and angiogenic responses in in vitro and in vivo assays. Overall, we found many similarities but also some important differences between hiPSC-derived and primary ECs. Assessment of vasculogenic responses in vivo showed little difference between primary ECs and hiPSC-ECs with regard to functional blood vessel formation, which may be important in future regenerative medicine applications requiring vascularization. In this article, Orlova and colleagues show that hiPSC-ECs have similar features to primary ECs but also show some differences. hiPSC-ECs exhibited higher barrier function, lower expression of pro-inflammatory adhesive receptors, and more stringent stromal cell requirements. Importantly, healthy control CD31+ hiPSC-ECs showed high consistency between different batches and lines, forming a good basis for disease modeling applications

Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo

Human umbilical cord blood (CB) has attracted much attention as a reservoir for functional hematopoietic stem and progenitor cells, and, recently, as a source of blood-borne fibroblasts (CB-BFs). Previously, we demonstrated that bone marrow stromal cell (BMSC) and CB-BF pellet cultures make cartilage in vitro. Furthermore, upon in vivo transplantation, BMSC pellets remodelled into miniature bone/marrow organoids. Using this in vivo model, we asked whether CB-BF populations that express characteristics of the hematopoietic stem cell (HSC) niche contain precursors that reform the niche. CB ossicles were regularly observed upon transplantation. Compared with BM ossicles, CB ossicles showed a predominance of red marrow over yellow marrow, as demonstrated by histomorphological analyses and the number of hematopoietic cells isolated within ossicles. Marrow cavities from CB and BM ossicles included donor-derived CD146-expressing osteoprogenitors and host-derived mature hematopoietic cells, clonogenic lineage-committed progenitors and HSCs. Furthermore, human CD34+ cells transplanted into ossicle-bearing mice engrafted and maintained human HSCs in the niche. Our data indicate that CB- BFs are able to recapitulate the conditions by which the bone marrow microenvironment is formed and establish complete HSC niches, which are functionally supportive of hematopoietic tissue

The characteristics of adjacent anatomy of mandibular third molar germs: a CBCT pilot study in patients with Osteogenesis Imperfecta

(1) Objectives: The aim of our study was to investigate the anatomical features of lower third molar and its adjacent anatomical connections in type I Osteogenesis Imperfecta (OI) patients through cone beam computed tomography (cbct). (2) Methods: The study was conducted among 25 patients, 13 patients with type I OI and 12 control patients (individuals with no disorders and no treatment); average age was 15.44 ± 2.06, 23 third molar germs for each group. The germs have been compared to the parameters using the Mann-Whitney test. A chi-square test was also used to investigate the correlation between the status case/control and tooth development stage. (3) Results: Mann-Whitney test showed significant differences between cases and controls: diameter of the tooth germ in toto (U = 93.5; p < 0.001), tooth development stage, (U = 145; p < 0.01), roots length (U = 44.5; p < 0.01), cementoenamel junction diameter (U = 157.5; p < 0.05), size of the pulp chamber (U = 95.5; p < 0.05). Type I OI is not associated with the relationship between the germ of mandibular third molar and alveolar canal on axial plane (χ2 = 4.095; p = 0.129), and parasagittal (χ2 = 4.800; p = 0.091). The association between type I OI and relationship with the germ of mandibular third molar and alveolar canal on the coronal plane has been significant (χ2 = 9.778; p < 0.05) as the perforation of the lingual cortical bone in the region of mandibular third molar tooth germ (χ2 = 11.189; p < 0.01). (4) Conclusions: The results confirm the cbct accuracy in the evaluation of bone density in type I OI patients giving also the opportunity to study the tridimensional anatomy of germs and the adjacent anatomical structures in order to avoid any perioperative complications

Establishment of bone marrow and hematopoietic niches in vivo by reversion of chondrocyte differentiation of human bone marrow stromal cells

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Unilateral isolated primary cutaneous amyloidosis of the external auditory canal

Isolated primary cutaneous amyloidosis (PCA) of the external ear is extremely rare. We describe the case of a 65-year-old woman presenting with itching within the left external auditory canal (EAC). Otoscopy revealed a 3 mm whitish lesion involving the cartilaginous portion of the left EAC. The lesion was excised. Histological and immunohistochemical features were consistent with keratinic amyloidosis. A clinical workup was negative for systemic amyloidosis. As far as we know, only nine cases of PCA exclusively involving the EAC have been reported. The frequent occurrence of itching in these patients and the keratinic nature of the amyloid support the role of chronic stimulation/irritation in the pathogenesis of isolated amyloidosis the EAC

Sporadic High-Grade Malignant Peripheral Nerve Sheath Tumor of the Hypoglossal Nerve

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"Non-phosphaturic" variant of phosphaturic mesenchymal tumor of the middle ear expressing multiple phosphatonins

Phosphaturic mesenchymal tumors (PMTs) are rare tumors commonly arising in soft tissues and bones. They are the main cause of tumor-induced osteomalacia (TIO), a paraneoplastic syndrome caused by production of FGF23 and other phosphatonins. “Non-phosphaturic” variant of PMTs (i.e., not associated with TIO) have been also reported. We describe a patient with a PMT of the middle ear, a very rare site for PMTs, in which TIO failed to develop although three phosphatonins were expressed

Postextractive alveolar ridge preservation using L-PRF: clinical and histological evaluation

Leukocyte- and platelet-rich fibrin (L-PRF) is an autologous platelet concentrate rich in growth factors and plasma proteins, obtained by centrifugation of patient whole blood, and widely used in oral surgery. This report describes a case of alveolar ridge preservation with L-PRF membranes. Postextractive alveolar healing was then assessed through a histologic and histomorphometric analysis. A patient requiring tooth extraction and subsequent implant rehabilitation was treated with simple extraction and socket filling with L-PRF membranes. Implant placement was performed at 3 months, and a bone biopsy was obtained for histomorphometric analysis. Histological examination of the grafted sites showed that the use of L-PRF could achieve good results in terms of bone dimension and quality and soft tissue healing. The results of this study support the use of L-PRF membranes to preserve hard and soft tissues after tooth extraction