For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

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The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics

Osteoimmunology is an interdisciplinary research field focused on the molecular understanding of the interplay between the immune and skeletal systems. Although osteoimmunology started with the study of the immune regulation of osteoclasts, its scope has been extended to encompass a wide range of molecular and cellular interactions, including those between osteoblasts and osteoclasts, lymphocytes and osteoclasts, and osteoblasts and haematopoietic cells. Therefore, the two systems should be understood to be integrated and operating in the context of the 'osteoimmune' system, a heuristic concept that provides not only a framework for obtaining new insights by basic research, but also a scientific basis for the discovery of novel treatments for diseases related to both systems.

Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems

Functions of RANKL/RANK/OPG in bone modeling and remodeling.

Transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-β/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-β/BMPs is specifically through both canonical Smad-dependent pathways (TGF-β/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-β/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-β/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-β/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-β/BMP signaling. This review also highlights the different modes of cross-talk between TGF-β/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation.

/pdf/tgf-b-and-bmp-signaling-in-osteoblast-differentiation-and-amp8wqpepp.pdf

TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation

Paired box protein 5 (Pax5) is a crucial transcription factor responsible for B-cell lineage specification and commitment. In this study, we identified a negative role of Pax5 in osteoclastogenesis. The expression of Pax5 was time-dependently downregulated by receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) stimulation in osteoclastogenesis. Osteoclast (OC) differentiation and bone resorption were inhibited (68.9% and 48% reductions, respectively) by forced expression of Pax5 in OC lineage cells. Pax5 led to the induction of antiosteoclastogenic factors through downregulation of B lymphocyte-induced maturation protein 1 (Blimp1). To examine the negative role of Pax5 in vivo, we generated Pax5 transgenic (Pax5Tg) mice expressing the human Pax5 transgene under the control of the tartrate-resistant acid phosphatase (TRAP) promoter, which is expressed mainly in OC lineage cells. OC differentiation and bone resorption were inhibited (54.2-76.9% and 24.0-26.2% reductions, respectively) in Pax5Tg mice, thereby contributing to the osteopetrotic-like bone phenotype characterized by increased bone mineral density (13.0-13.6% higher), trabecular bone volume fraction (32.5-38.1% higher), trabecular thickness (8.4-9.0% higher), and trabecular number (25.5-26.7% higher) and decreased trabecular spacing (9.3-10.4% lower) compared to wild-type control mice. Furthermore, the number of OCs was decreased (48.8-65.3% reduction) in Pax5Tg mice. These findings indicate that Pax5 plays a negative role in OC lineage specification and commitment through Blimp1 downregulation. Thus, our data suggest that the Pax5-Blimp1 axis is crucial for the regulation of RANKL-induced osteoclastogenesis.

https://www.mdpi.com/1422-0067/22/4/2097/pdf

Pax5 Negatively Regulates Osteoclastogenesis through Downregulation of Blimp1.

Immunohistochemical Analysis of the Distribution of RANKL-Expressing Cells and the Expression of Osteoclast-Related Markers in Giant Cell Tumor of Bone

Effects of anti-RANKL antibodies administered to pregnant mice on bone and tooth development in neonates.

Ionomycin and A23187 which are known as calcium ionophores, induced osteoclastic differentiation in the coculture of mouse bone marrow cells and primary osteoblasic cells. Osteoclast-like cells induced by these agents appeared as multinucleated giant cells with tartrate resistant acid phosphatase activity, and formed resorption lacunae on dentine slices. Calcium ionophores are reported to increase intracellular Ca2+ level. Therefore, these results suggests that osteoclastic differentiation induced by calcium ionophore is a result of the increase of intracellular Ca2+ level, and that high Ca2+ level may be a part of signaling pathways that induce differentiation of osteoclast progenitor to osteoclast.

Masamichi Takami

Papers

Pax5 Negatively Regulates Osteoclastogenesis through Downregulation of Blimp1.

Immunohistochemical Analysis of the Distribution of RANKL-Expressing Cells and the Expression of Osteoclast-Related Markers in Giant Cell Tumor of Bone

Effects of anti-RANKL antibodies administered to pregnant mice on bone and tooth development in neonates.

Increase of Intracellular Ca 2+ Level Induces Osteoclast- Like Cell Formation in Coculture of Mouse Bone Marrow Cells and Osteoblastic Cells

The Establishment of an Assay System for the Compounds Affecting Actin Ring Formation of Murine Osteoclast-Like Cells