Here, we demonstrate that the Ca(2+)/calmodulin-sensitive phosphatase calcineurin is a necessary downstream mediator for osteoclast differentiation. Using quantitative PCR, we detected the calcineurin isoforms Aalpha, Abeta, Agamma (catalytic), and B1 (regulatory) in osteoclast precursor RAW-C3 cells. We found that, although the expression of these isoforms remained relatively unchanged during ...

Osteoclast-stimulating factor increases osteoclast formation and bone resorption through a cellular signal transduction cascade, possibly by its interaction with c-Src or related family members. Crystals of human osteoclast-stimulating factor were obtained by the hanging-drop vapour-diffusion method using ammonium sulfate as a precipitant. The crystals are primitive orthorhombic and belong to P...

Osteoclast formation is dependent on the ability of TGF-beta to enable receptor activator of NF-kappaB ligand (RANKL)-induced commitment of hemopoietic precursors to the osteoclastic lineage. The mechanism by which TGF-beta enables formation is unknown. One possibility is that TGF-beta opposes Janus kinase (JAK)/STAT signals generated by inhibitory cytokines such as IFN-beta. The JAK/STAT pathw...

TNF induces bone loss in common bone diseases by promoting osteoclast formation directly and indirectly, but it also limits osteoclast formation by inducing expression of NF-κB p100. Osteoclast precursors (OCPs) are derived from M1 (inflammatory) and M2 (resident) macrophages. However, it is not known if TNF stimulates or limits osteoclast formation through regulation of M1 or M2 differentiatio...

Experiments in vivo have established that tooth eruption fails in the absence of parathyroid hormone (PTH)-related protein (PTHrP) action in the microenvironment of the tooth because of the failure of osteoclastic bone resorption on the coronal tooth surface to form an eruption pathway. To elucidate the effects of PTHrP on osteoclast regulation in this environment, we established primary cultur...

Metastatic breast cancer causes destruction of significant amounts of bone, and, although bone is the most likely site of breast cancer metastasis, little is understood about interactions between tumor cells and boneresorbing osteoclasts. We have investigated the paracrine factors produced by breast cancer cells that are involved in increasing osteoclast activity. We have determined by immunoas...

During bone resorption, a large amount of inorganic phosphate (P(i)) is generated within the osteoclast hemivacuole. The mechanisms involved in the disposal of this P(i) are not clear. In the present study, we investigated the efflux of P(i) from osteoclast-like cells. P(i) efflux was activated by acidic conditions in osteoclast-like cells derived by the treatment of RAW264.7 cells with recepto...

Bisphosphonates (BPs) such as pamidronate are used to treat bone destructive diseases and act by inhibiting bone resorption by osteoclasts, thereby improving bone quality. In contrast, BPs were shown to stimulate osteoclast formation and resorption at the mouse molar root. Periodontal ligament (PDL) fibroblasts could be seen as the mediators of osteoclast formation at this location. Here, we in...

INTRODUCTION The aim of this study is to determine whether regulation of the expression level of fms-like tyrosine kinase-4 (Flt-4) is related to osteoclast differentiation. MATERIAL AND METHODS Osteoclast formation and differentiation of mouse bone marrow cells and RAW264.7 cells were performed. To induce osteoclast differentiation, RANKL (50 ng/ml) with or without vascular endothelial growt...

Langerhans cell histiocytosis (LCH) is a disease that can involve one or multiple organ systems characterized by an accumulation of CD1a(+) Langerhans-like cells as well as several other myeloid cell types. The precise origin and role of one of these populations, the multinucleated giant cell (MGC), in this disease remains unknown. This work shows that in three different lesional tissues, bone,...