Follicle-stimulating hormone does not impact male bone mass in vivo or human male osteoclasts in vitro.

Bone loss in the elderly is mainly caused by osteoclast-induced bone resorption thought to be causally linked to the decline in estrogen and testosterone levels in females and males. Recently, involvement of follicle stimulating-hormone (FSH) in this process has been suggested to explain in part the etiology of the disease in females, whereas its role in males has never been examined. In this study, the direct impact of FSH on bone mass of 16-week-old C57BL/6J male mice by either daily intermittent application of 6 or 60 mug/kg of FSH or continuous delivery via miniosmotic pump of a dose of 6 mug/kg over the course of a month was assessed.

Everolimus suppresses cancellous bone loss, bone resorption, and cathepsin K expression by osteoclasts.

The proliferation inhibitor of the macrolide class, everolimus, is a drug shown to be effective in the prevention of organ transplant rejection and to have a potential in the treatment of rheumatoid arthritis and certain cancers. As these diseases or their current treatments are associated with bone loss, we examined the effect of everolimus on mouse and human bone cells in vitro and on bone in an ovariectomized (OVX) rat model. Everolimus potently inhibited primary mouse and human osteoclast activity in the pit assay (IC50 values of 0.

Human primary osteoclasts: in vitro generation and applications as pharmacological and clinical assay.

Osteoclasts are cells of hematopoietic origin with a unique property of dissolving bone; their inhibition is a principle for treatment of diseases of bone loss. Protocols for generation of human osteoclasts in vitro have been described, but they often result in cells of low activity, raising questions on cell phenotype and suitability of such assays for screening of bone resorption inhibitors. Here we describe an optimized protocol for the production of stable amounts of highly active human osteoclasts.

Transcriptional program of mouse osteoclast differentiation governed by the macrophage colony-stimulating factor and the ligand for the receptor activator of NFkappa B.

Cytokines macrophage colony stimulating factor (M-CSF) and the receptor activator of NFkappaB ligand (RANKL) induce differentiation of bone marrow hematopoietic precursor cells into bone-resorbing osteoclasts without the requirement for stromal cells of mesenchymal origin. We used this recently described mouse cell system and oligonucleotide microarrays representing about 9,400 different genes to analyze gene expression in hematopoietic cells undergoing differentiation to osteoclasts. The ability of microarrays to detect the genes of interest was validated by showing expression and expected regulation of several osteoclast marker genes.