Editorial: Special Issue on “Molecular Mechanisms Regulating Osteoclastogenesis”

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

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

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

Copresentation of BMP-6 and RGD ligands enhances cell adhesion and BMP-mediated signaling

We report on the covalent immobilization of bone morphogenetic protein 6 (BMP-6) and its co-presentation with integrin ligands on a nanopatterned platform to study cell adhesion and signaling responses which regulate the transdifferentiation of myoblasts into osteogenic cells. To immobilize BMP-6, the heterobifunctional linker MU-NHS is coupled to amine residues of the growth factor; this prevents its internalization while ensuring that its biological activity is maintained. Additionally, to allow cells to adhere to such platform and study signaling events arising from the contact to the surface, we used click-chemistry to immobilize cyclic-RGD carrying an azido group reacting with PEG-alkyne spacers via copper-catalyzed 1,3-dipolar cycloaddition. We show that the copresentation of BMP-6 and RGD favors focal adhesion formation and promotes Smad 1/5/8 phosphorylation. When presented in low amounts, BMP-6 added to culture media of cells adhering to the RGD ligands is less effective than BMP-6 immobilized on the surfaces in inducing Smad complex activation and in inhibiting myotube formation. Our results suggest that a local control of ligand density and cell signaling is crucial for modulating cell response

A soft supernumerary hand for rehabilitation in sub-acute stroke: a pilot study

: In patients with subacute stroke, task specific training (TST) has been shown to accelerate functional recovery of the upper limb. However, many patients do not have sufficient active extension of the fingers to perform this treatment. In these patients, here we propose a new rehabilitation technique in which TST is performed through a soft robotic hand (SoftHand-X). In short, the extension of the robotic fingers is controlled by the patient through his residual, albeit minimal, active extension of the fingers or wrist, while the patient was required to relax the muscles to achieve full flexion of the robotic fingers. TST with SoftHand-X was attempted in 27 subacute stroke patients unable to perform TST due to insufficient active extension of the fingers. Four patients (14.8%) were able to perform the proposed treatment (10 daily sessions of 60 min each). They reported an excellent level of participation. After the treatment, both clinical score of spasticity and its electromyographic correlate (stretch reflex) decreased. In subacute stroke patients, TST using SoftHand-X is a well-accepted treatment, resulting in a decrease of spasticity. At present, it can be applied only in a small proportion of the patients who cannot perform conventional TST, though extensions are possible

Time-course changes in rat cerebral cortex subcellular distribution of the cyclic-AMP binding after treatment with selective serotonin reuptake inhibitors

Pharmacological investigations have suggested the involvement of the cAMP transduction pathway in the action of antidepressant drugs and in the pathophysiology of mood disorders. We have extended these studies to determine the time-related effects of two selective serotonin reuptake inhibitors, fluvoxamine (15 mg/kg) and paroxetine (5 mg/kg), on the cAMP-binding in rat cerebral cortex, after short and long-term treatments. Photoaffinity labelling experiments with 8-N(3)-[(32)P]cAMP were carried out in cerebrocortical soluble (S1 or S2) and microtubule fractions. In our conditions, both SSRIs administered for 5 days were unable to affect the cAMP-binding in S1, S2, and in microtubule fractions. After 12 days of treatment, paroxetine and fluvoxamine significantly enhanced the cAMP-binding to the 54 kDa protein, corresponding to the type II regulatory subunit of PKA (RII), in the S1 and microtubule fractions. Any modification in respect to controls was observed in S2, the soluble fraction devoid of microtubules. After 21 days of treatment no changes were observed in the soluble S1 fraction and in microtubules, but the cAMP-binding to the RII subunit was found to be significantly higher in the S2 fraction. The high concentration of RII, demonstrated first in microtubules (12 days) and then in the cytosol (21 days), could be the result of a time-related effect of SSRIs on PKA and its translocation from microtubule compartment to the cytosol. The present findings seem to demonstrate the capacity of SSRIs to modulate the subcellular distribution of PKA and support the involvement of the cAMP pathway in the mechanism of action of these drugs