TNFα inhibits the development of osteoclasts through osteoblast-derived GM-CSF

Inflammatory cytokines such as tumor necrosis factor-alpha (TNFα) are potent stimulators of osteoclast formation and bone resorption and are frequently associated with pathologic bone metabolism. The cytokine exerts specific effects on its target cells and constitutes a part of the cellular microenvironment. Previously, TNFα was demonstrated to inhibit the development of osteoclasts in vitro via an osteoblast-mediated pathway. In the present study, the molecular mechanisms of the inhibition of osteoclastogenesis were investigated in co-cultures of osteoblasts and bone marrow cells (BMC) and in cultures of macrophage-colony stimulating factor (M-CSF) dependent, non-adherent osteoclast progenitor cells (OPC) grown with M-CSF and receptor activator of NF-κB ligand (RANKL). Granulocyte-macrophage colony stimulating factor (GM-CSF), a known inhibitor of osteoclastogenesis was found to be induced in osteoblasts treated with TNFα and the secreted protein accumulated in the supernatant. Dexamethasone (Dex), an anti-inflammatory steroid, caused a decrease in GM-CSF expression, leading to partial recovery of osteoclast formation. Flow cytometry analysis revealed that in cultures of OPC, supplemented with 10% conditioned medium (CM) from osteoblasts treated with TNFα/1,25(OH)(2)D(3), expression of RANK and CD11c was suppressed. The decrease in RANK expression may be explained by the finding, that GM-CSF and the CM from wt osteoblasts were found to suppress the expression of c-Fos, Fra-1, and Nfatc-1. The failure of OPC to develop into CD11c(+) dendritic cells suggests that cell development is not deviated to an alternative differentiation pathway, but rather, that the monocytes are maintained in an undifferentiated, F4/80(+), state. The data further implies possible interactions among inflammatory cytokines. GM-CSF induced by TNFα acts on early hematopoietic precursors, inhibiting osteoclastogenesis while acting as the growth factor for M-CSF independent inflammatory macrophages. These in turn may condition a microenvironment enhancing osteoclast differentiation and bone resorption upon migration of the OPC from circulation to the bone/bone marrow compartment.

[Blood flow assessment with magnetic resonance imaging after 1.9 μm diode laser assisted arterial micronastomoses]

The most important factor for successful free-flap transfer and replantations is a well-executed anastomosis. The aim of this study is to assess blood flow after laser assisted arterial microanastomosis (LAMA) using a 1.9 μm diode laser.

[The image of the dentist. Part 1: Results of a literature search]

The dentist enjoys a high degree of professional independence. He is seen as reliable and productive at work while carrying a big responsibility. His foremost social responsibility is to treat patients suffering from toothache and to promote oral health prevention for all people, regardless of their social status. At the same time, the dentist is prestigious, respected and honest. Comparable to other professions, however, dentistry is under public pressure. Media often associate the dental profession with negative properties such as sadism, immorality, or madness. Does the image of the dental profession suffer in this context? Our first article discusses the environmental factors which are identifiable to influence both each dentist and ultimately the whole image of dentistry.