Baricitinib ameliorates inflammatory and neuropathic pain in collagen antibody-induced arthritis mice by modulating the IL-6/JAK/STAT3 pathway and CSF-1 expression in dorsal root ganglion neurons.

Background: Janus kinase (JAK) inhibitors, such as baricitinib, are widely used to treat rheumatoid arthritis (RA). Clinical studies show that baricitinib is more effective at reducing pain than other similar drugs. Here, we aimed to elucidate the molecular mechanisms underlying the pain relief conferred by baricitinib, using a mouse model of arthritis.

Inflammatory diseases causing joint and bone destruction: rheumatoid arthritis and hemophilic arthropathy.

Various diseases and conditions cause joint disorders. Osteoarthritis (OA) is characterized by the degeneration of articular cartilage, synovitis, and anabolic changes in surrounding bone tissues. In contrast, rheumatoid arthritis (RA) and hemophilic arthropathy (HA) display marked destruction of bone tissues caused by synovitis.

Periosteal stem cells control growth plate stem cells during postnatal skeletal growth.

The ontogeny and fate of stem cells have been extensively investigated by lineage-tracing approaches. At distinct anatomical sites, bone tissue harbors multiple types of skeletal stem cells, which may independently supply osteogenic cells in a site-specific manner. Periosteal stem cells (PSCs) and growth plate resting zone stem cells (RZSCs) critically contribute to intramembranous and endochondral bone formation, respectively.

Plasma cells promote osteoclastogenesis and periarticular bone loss in autoimmune arthritis.

In rheumatoid arthritis (RA), osteoclastic bone resorption causes structural joint damage as well as periarticular and systemic bone loss. Periarticular bone loss is one of the earliest indices of RA, often preceding the onset of clinical symptoms via largely unknown mechanisms. Excessive osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL) expressed by synovial fibroblasts causes joint erosion, whereas the role of RANKL expressed by lymphocytes in various types of bone damage has yet to be elucidated.

Stepwise cell fate decision pathways during osteoclastogenesis at single-cell resolution.

Osteoclasts are the exclusive bone-resorbing cells, playing a central role in bone metabolism, as well as the bone damage that occurs under pathological conditions. In postnatal life, haematopoietic stem-cell-derived precursors give rise to osteoclasts in response to stimulation with macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand, both of which are produced by osteoclastogenesis-supporting cells such as osteoblasts and osteocytes. However, the precise mechanisms underlying cell fate specification during osteoclast differentiation remain unclear.

The role of bone cells in immune regulation during the course of infection.

Bone homeostasis depends on a balance between osteoclastic bone resorption and osteoblastic bone formation. Bone cells are regulated by a variety of biochemical factors, such as hormones and cytokines, as well as various types of physical stress. The immune system affects bone, since such factors are dysregulated under pathologic conditions, including infection.

Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis.

Bone is one of the preferred sites for the metastasis of malignant tumours, such as breast cancer, lung cancer and malignant melanoma. Tumour cells colonizing bone have the capacity to induce the expression of receptor activator of nuclear factor-κB ligand (RANKL), which promotes osteoclast differentiation and activation. Tumour-induced osteoclastic bone resorption leads to a vicious cycle between tumours and bone cells that fuels osteolytic tumour growth, causing bone pain and hypercalcaemia.

Arginine methylation controls the strength of γc-family cytokine signaling in T cell maintenance.

The methylation of arginine residues in proteins is a post-translational modification that contributes to a wide range of biological processes. Many cytokines involved in T cell development and activation utilize the common cytokine receptor γ-chain (γc) and the kinase JAK3 for signal transduction, but the regulatory mechanism that underlies the expression of these factors remains unclear. Here we found that the arginine methyltransferase PRMT5 was essential for the maintenance of invariant natural killer T cells (iNKT cells), CD4 T cells and CD8 T cells.

Overview of Osteoimmunology.

Aberrant or prolonged immune responses often affect bone metabolism. The investigation on bone destruction observed in autoimmune arthritis contributed to the development of research area on effect of the immune system on bone. A number of reports on bone phenotypes of immunocompromised mice indicate that the immune and skeletal systems share various molecules, including transcription factors, signaling molecules, and membrane receptors, suggesting the interplay between the two systems.

[Aberrant bone remodeling during sepsis.].

Sepsis is a systemic inflammatory response syndrome that occurs upon severe bacterial infection. Although the development of early treatment for sepsis improves the survival rate of sepsis patients, in the subacute phase, certain patients suffer from secondary infection due to immunosuppression. It has been reported that one of the causes of the immunocompromised state during sepsis is lymphopenia.

Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems.

The immune and skeletal systems share a variety of molecules, including cytokines, chemokines, hormones, receptors, and transcription factors. Bone cells interact with immune cells under physiological and pathological conditions. Osteoimmunology was created as a new interdisciplinary field in large part to highlight the shared molecules and reciprocal interactions between the two systems in both heath and disease.

LOX Fails to Substitute for RANKL in Osteoclastogenesis.

Osteoclasts are the exclusive bone-resorbing cells that have a central role in bone homeostasis as well as bone destruction in cancer and autoimmune disease. Both mouse and human genetic studies have clearly proven that receptor activator of NF-κB ligand (RANKL; encoded by the Tnfsf11 gene) and its receptor RANK are essential for osteoclastogenesis. Although there have been several reports on RANKL-independent osteoclastogenesis, previous studies have never provided in vivo evidence showing RANKL can be substituted by other molecules using RANKL- or RANK-deficient genetic backgrounds.

Sepsis-Induced Osteoblast Ablation Causes Immunodeficiency.

Sepsis is a host inflammatory response to severe infection associated with high mortality that is caused by lymphopenia-associated immunodeficiency. However, it is unknown how lymphopenia persists after the accelerated lymphocyte apoptosis subsides. Here we show that sepsis rapidly ablated osteoblasts, which reduced the number of common lymphoid progenitors (CLPs).

[Analysis of Musculoskeletal Systems and Their Diseases. Bone metabolism and intercellular network].

Bone is an active organ under continuous bone remodeling that consists of bone resorption and synthesis. The process requires precise communication among bone cells including osteoclasts, osteoblasts and osteocytes. However, the detailed mechanisms of bone cell interactions have been poorly understood.

[Bone and Stem Cells. Immune cell regulation by the bone marrow niche].

Adult hematopoietic stem cells (HSCs) are maintained in the bone marrow and give rise to all blood cell types. The maintenance and the differentiation of blood cells including immune cells are essential for host defense and oxygen delivery. HSCs are maintained in microenvironments called stem cell niches, which consists of various cell types in bone marrow.

MCA1 and MCA2 that mediate Ca2+ uptake have distinct and overlapping roles in Arabidopsis.

Ca(2+) is important for plant growth and development as a nutrient and a second messenger. However, the molecular nature and roles of Ca(2+)-permeable channels or transporters involved in Ca(2+) uptake in roots are largely unknown. We recently identified a candidate for the Ca(2+)-permeable mechanosensitive channel in Arabidopsis (Arabidopsis thaliana), named MCA1.

A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity.

Airway hypersensitive reaction (AHR) is an animal model for asthma, which is caused or enhanced by environmental factors such as allergen exposure. However, the precise mechanisms that drive AHR remain unclear. We identified a novel subset of natural killer T (NKT) cells that expresses the interleukin 17 receptor B (IL-17RB) for IL-25 (also known as IL-17E) and is essential for the induction of AHR.

Arabidopsis plasma membrane protein crucial for Ca2+ influx and touch sensing in roots.

Plants can sense and respond to mechanical stimuli, like animals. An early mechanism of mechanosensing and response is speculated to be governed by as-yet-unidentified sensory complexes containing a Ca(2+)-permeable, stretch-activated (SA) channel. However, the components or regulators of such complexes are poorly understood at the molecular level in plants.