Editorial: Special Issue on “Molecular Mechanisms Regulating Osteoclastogenesis”

Bone is an active tissue that remodels continuously throughout life [...]

Role of the PspA protein in maintaining membrane integrity in Escherichia coli

Bacteria have successfully colonized various hostile environments by evolving stress response mechanisms, allowing them to sense and adapt to adverse conditions. In E. coli, the Psp (phage-shock protein) system is induced by a wide range of membrane stresses. PspA, a peripheral membrane protein of the Psp system, is known to act as a regulator for the transcription factor PspF and work in vitro suggests that it may contribute to the maintenance of the Proton Motive Force and translocation of proteins. The conservation of PspA across the three domains of life suggests it has a pivotal role in preserving membrane integrity, although its specific mechanism of action remains to be elucidated. To better understand the behaviour of PspA in vivo and its interactions with other proteins, a mutant E. coli strain expressing PspA fused with a Venus reporter protein was exposed to membrane stress. Microscopy showed that Venus-PspA changed its behaviour when under stress, forming brighter and less mobile spots at the cell periphery. PspA interactions with other proteins were demonstrated by epitope tag-based pull-down, revealing different interaction partners following stress induction. Further LC/MS/MS analyses of the isolated proteins identified interactions with a specific set of proteins involved in stress response, translation and translocation of proteins. These newly-discovered interactions suggest that PspA is involved in cellular functions that were not previously suspected. My working model is that PspA helps to organise centresfor the localised assembly and translocation of membrane and secreted proteins

Renoprotezione farmacologica nella nefropatia cronica proteinurica

Background. Proteinuria of Chronic Kidney Disease (CKD) is frequently associated to dyslipidemia, that increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as ACEi or ARB, which effectively reduce proteinuria. Moreover, clinical and experimental studies provided evidence that statin exerts renoprotective effect, but their role in renal outcomes is still unclear. Methods. In this prospective, randomized trial, we evaluated if statin, combined to ACEi and ARB, more effectively than ACEi/ARB alone reduce proteinuria, and if this effect translate in a reduction of renal function decline. After 2 months of Benazepril/Valsartan combined therapy, 186 patients were randomized to 6 months Fluvastatin (80 mg/die) YES or NO additional therapy. Results. Benazepril/Valsartan therapy significantly and safely reduced proteinuria, total and LDL cholesterol. Fluvastatin addition optimised blood pressure control and effectively reduced proteinuria in nephrotic patients, in particular with diabetes. Renal function stabilised during Benazepril/Valsartan therapy alone, while more rapidly decreased with Fluvastatin addition, possibly via blood pressure reduction. Conclusion. In CKD patients with dyslipidemia, double RAS blockade is renoprotective and improves lipid profile through amelioration of nephrotic syndrome. Fluvastatin effectively improves renal outcomes only in nephrotic patients. Thus, Fluvastatin therapy must be reserved to this clinical setting

The Interplay between the Bone and the Immune System

In the last two decades, numerous scientists have highlighted the interactions between bone and immune cells as well as their overlapping regulatory mechanisms. For example, osteoclasts, the bone-resorbing cells, are derived from the same myeloid precursor cells that give rise to macrophages and myeloid dendritic cells. On the other hand, osteoblasts, the bone-forming cells, regulate hematopoietic stem cell niches from which all blood and immune cells are derived. Furthermore, many of the soluble mediators of immune cells, including cytokines and growth factors, regulate the activities of osteoblasts and osteoclasts. This increased recognition of the complex interactions between the immune system and bone led to the development of the interdisciplinary osteoimmunology field. Research in this field has great potential to provide a better understanding of the pathogenesis of several diseases affecting both the bone and immune systems, thus providing the molecular basis for novel therapeutic strategies. In these review, we reported the latest findings about the reciprocal regulation of bone and immune cells

Bone-immune cell crosstalk: Bone diseases

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma