Interferons (IFNs) have been shown to negatively regulate osteoclastogenesis. In a proteomic study to assess protein expression during osteoclastogenesis, we discovered that the expression level of Jak1 was significantly decreased during the early stage of osteoclast differentiation from mouse bone marrow macrophages (BMMs) upon stimulation with receptor activator of nuclear factor kappaB ligan...

Osteoclast differentiation and function are required for normal bone resorption and remodeling (1, 2). The mature osteoclast polykaryon arises from marrowresiding precursor cells of hematopoietic origin, believed to be monocytes/macrophages (1–3). Early studies have shown that cocultures of these precursor cells with stromal/osteoblastic cells in the presence of hormonal steroids led to differe...

An abnormal increase in osteoclast differentiation and activation results in various bone-resorptive diseases, including periodontitis, rheumatoid arthritis, and osteoporosis. Chemical compounds containing pyrimidine ring have been shown to regulate a variety of biological processes. Therefore, in order to identify an antiresorptive agent, we synthesized a series of pyrimidine ring-containing c...

Chrysanthemum zawadskii Herbich var. latilobum Kitamura, known as "Gujulcho" in Korea, has been used in traditional medicine to treat various inflammatory diseases, including rheumatoid arthritis. However, these effects have not been tested on osteoclasts, the bone resorbing cells that regulate bone metabolism. Here, we investigated the effects of C. zawadskii Herbich var. latilobum Kitamura et...

Microtubule organization and lysosomal secretion are both critical for the activation and function of osteoclasts, highly specialized polykaryons that are responsible for bone resorption and skeletal homeostasis. Here, we have identified a novel interaction between microtubule regulator LIS1 and Plekhm1, a lysosome-associated protein implicated in osteoclast secretion. Decreasing LIS1 expressio...

INTRODUCTION Osteoclasts are multinucleated cells that are derived from the hematopoietic myeloid/monocyte lineage via the action of M-CSF and receptor activator of NF-κB ligand (RANKL) (1). Binding of RANKL to RANK activates and/or induces expression of the transcription factors NF-κB, AP-1, and NFAT2, which are important for osteoclast differentiation (1, 2). Fusion-induced osteoclast formati...

BACKGROUND Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-gamma. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the osteoclastogenesis process remains unclear. METHODOLOGY/PRINCIPAL FINDINGS In the present study, we have shown that I...

Context: The discovery of the receptor activator for nuclear factor B (RANK) ligand (RANKL)/RANK signaling pathway has marked a major advance in our understanding of the mechanisms controlling osteoclastogenesis. RANKL, expressed by preosteoblasts and stromal cells, binds to RANK, expressed by cells of the osteoclast lineage, inducing a signaling cascade leading to the differentiation and fusio...

The process of osteoclast differentiation and resorption is fine-tuned by signal pathways, which need to be further elucidated. The aim of this study was to explore the possible connections between NF-kappaB and Notch in RANKL-induced osteoclast activity. To this end, RANKL was used to stimulate mouse osteoclast precursor cell line RAW264.7. The number of multinucleated TRAP+ osteoclasts was co...

The prevention or therapeutic treatment of loss of bone mass is an important means of improving the quality of life for patients with disorders related to osteoclast-mediated bone loss. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Continus coggygria), exhibits various biological activities, but its effect on osteoclast differentiation is unknown. In this study, fisetin dose-...