Activated invariant NKT cells regulate osteoclast development and function.

Invariant NKT (iNKT) cells modulate innate and adaptive immune responses through activation of myeloid dendritic cells and macrophages and via enhanced clonogenicity, differentiation, and egress of their shared myeloid progenitors. Because these same progenitors give rise to osteoclasts (OCs), which also mediate the egress of hematopoietic progenitors and orchestrate bone remodeling, we hypothesized that iNKT cells would extend their myeloid cell regulatory role to the development and function of OCs. In this study, we report that selective activation of iNKT cells by α-galactosylceramide causes myeloid cell egress, enhances OC progenitor and precursor development, modifies the intramedullary kinetics of mature OCs, and enhances their resorptive activity.

Glycine and glycine receptor signalling in non-neuronal cells.

Glycine is an inhibitory neurotransmitter acting mainly in the caudal part of the central nervous system. Besides this neurotransmitter function, glycine has cytoprotective and modulatory effects in different non-neuronal cell types. Modulatory effects were mainly described in immune cells, endothelial cells and macroglial cells, where glycine modulates proliferation, differentiation, migration and cytokine production.

TGF-beta coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival.

To better understand the roles of TGF-beta in bone metabolism, we investigated osteoclast survival in response TGF-beta and found that TGF-beta inhibited apoptosis. We examined the receptors involved in promotion of osteoclast survival and found that the canonical TGF-beta receptor complex is involved in the survival response. The upstream MEK kinase TAK1 was rapidly activated following TGF-beta treatment.

Treg cells suppress osteoclast formation: a new link between the immune system and bone.

Objective: To investigate whether Treg cells can suppress osteoclast differentiation, and to define a new potential link between the immune system and the skeleton.

Methods: Regulatory CD4+,CD25+,Foxp3+ T cells were isolated and purified from the spleen and cocultured with CD11b+ osteoclast precursor cells isolated from bone marrow. Osteoclastogenesis and bone erosion were assessed by tartrate-resistant acid phosphatase staining and pit resorption assay, respectively.