Takeshi Miyamoto

Osteoclasts and dendritic cells are derived from monocyte/macrophage precursor cells; however, how their lineage commitment is regulated is unknown. This study investigated the differentiation pathways of osteoclasts and dendritic cells from common precursor cells at the single-cell level. Osteoclastogenesis induced by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappaB ligand (RANKL) or tumor necrosis factor-alpha (TNF-alpha) is completely inhibited by a

Controlling osteoclastogenesis is critical to maintain physiological bone homeostasis and prevent skeletal disorders. Although signaling activating nuclear factor of activated T cells 1 (NFATc1), a transcription factor essential for osteoclastogenesis, has been intensively investigated, factors antagonistic to NFATc1 in osteoclasts have not been characterized. Here, we describe a novel pathway that maintains bone homeostasis via two transcriptional repressors, B cell lymphoma 6 (Bcl6) and B lymp

Cell–cell fusion is a dynamic phenomenon promoting cytoskeletal reorganization and phenotypic changes. To characterize factors essential for fusion of macrophage lineage cells, we identified the multitransmembrane protein, osteoclast stimulatory transmembrane protein (OC-STAMP), and analyzed its function. OC-STAMP–deficient mice exhibited a complete lack of cell–cell fusion of osteoclasts and foreign body giant cells (FBGCs), both of which are macrophage-lineage multinuclear cells, although expr

Osteoclasts, which are responsible for bone resorption, are rare cells with only 2-3 cells seen per 1 mm3 of bone. However, the loss of function in osteoclasts, problems with their differentiation and decrease in their number lead to bone osteosclerosis/osteopetrosis. On the other hand, an increase in their number or function induces bone osteoporosis, indicating that osteoclasts play a pivotal role in bone homeostasis. It has been demonstrated that bone destruction and hypercalcemia induced by

Osteoclasts are multinuclear giant cells derived from osteoclast/macrophage/dendritic cell common progenitor cells. The most characteristic feature of osteoclasts is multinucleation resulting from cell-cell fusion of mononuclear osteoclasts. Osteoclast cell-cell fusion is considered essential for re-organization of the cytoskeleton, such as the actin-ring and ruffled boarder to seal the resorbing area and to secret protons, respectively, to resorb bone; the fusion process is thus critical for os

Identification of receptor activator of nuclear factor-kappaB (RANK) and RANK-ligand (RANKL) has provided new insights into the osteoclast differentiation pathway. Osteoclast precursor cells were isolated using monoclonal antibodies against c-Fms and RANK, and the effect of adherence on the in vitro differentiation and proliferation of these cells was examined in 2 different types of stromal-cell-free culture systems: a semisolid culture medium (a nonadherent system) and a liquid culture medium

Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that de-differ

Osteoporosis is a complex disease with various causes, such as estrogen loss, genetics, and aging. Here we show that a dominant-negative form of aldehyde dehydrogenase 2 (ALDH2) protein, ALDH2*2, which is produced by a single nucleotide polymorphism (rs671), promotes osteoporosis due to impaired osteoblastogenesis. Aldh2 plays a role in alcohol-detoxification by acetaldehyde-detoxification; however, transgenic mice expressing Aldh2*2 (Aldh2*2 Tg) exhibited severe osteoporosis with increased leve