The University of Osaka · Biochemistry, Genetics and Molecular Biology
Professor Tomohiko Murakami's research lab focuses on the molecular mechanisms underlying inflammatory responses and joint homeostasis, with a particular emphasis on the NLRP3 inflammasome, endoplasmic reticulum stress signaling, and cytokine-mediated cartilage destruction. The lab investigates key regulators such as calcium signaling, G protein subunits, and stress-responsive transcription factors like OASIS, aiming to uncover novel therapeutic targets for inflammatory and degenerative joint diseases. Their work integrates molecular biology, immunology, and in vivo disease models to elucidate pathogenic pathways in osteoarthritis and rheumatoid arthritis.
Figures are computed from collected data and may differ slightly.
The NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) inflammasome mediates production of inflammatory mediators, such as IL-1β and IL-18, and as such is implicated in a variety of inflammatory processes, including infection, sepsis, autoinflammatory diseases, and metabolic diseases. The proximal steps in NLRP3 inflammasome activation are not well understood. Here we elucidate a critical role for Ca(2+) mobilization in activation of the NLRP3 inf
When unfolded or misfolded proteins accumulate in the endoplasmic reticulum (ER), unfolded protein response (UPR) signals are transmitted from the ER to the nucleus and cytoplasm to facilitate protein folding. OASIS (old astrocyte specifically induced substance) is an ER stress transducer in astrocytes, a membrane-bound transcription factor that activates genes in the ER stress response. When unfolded proteins accumulate in the ER, OASIS is cleaved at the membrane to release its cytoplasmic doma
Inflammation is a pivotal response to a variety of stimuli, and inflammatory molecules such as cytokines have central roles in the pathogenesis of various diseases, including bone and joint diseases. Proinflammatory cytokines are mainly produced by immune cells and mediate inflammatory and innate immune responses. Additionally, proinflammatory cytokines accelerate bone resorption and cartilage destruction, resulting in the destruction of bone and joint tissues. Thus, proinflammatory cytokines ar
The NLRP3 inflammasome has important roles in the pathogenesis of various inflammatory diseases. However, the regulatory mechanisms of the NLRP3 inflammasome are not fully understood. In this study, we attempted to identify molecules that interact with NLRP3 upon its activation. We identified G protein subunit β 1 (GNB1), a downstream molecule of G protein-coupled receptors (GPCRs), which regulates the NLRP3 inflammasome activation. GNB1 was physically associated with NLRP3 via the pyrin domain
Proinflammatory cytokines play critical roles in the pathogenesis of joint diseases. Using a mass spectrometry-based cloning approach, we identified Semaphorin 4D (Sema4D) as an inflammatory cytokine that directly promoted cartilage destruction. <i>Sema4d</i>-deficient mice showed less cartilage destruction than wild-type mice in a model of rheumatoid arthritis. Sema4D induced a proinflammatory response in mouse articular chondrocytes characterized by the induction of proteolytic enzymes that de
Growth differentiation factor 5 (GDF5), a BMP family member, is highly expressed in the surface layer of articular cartilage. The GDF5 gene is a key risk locus for osteoarthritis and Gdf5-deficient mice show abnormal joint development, indicating that GDF5 is essential in joint development and homeostasis. In this study, we aimed to identify transcription factors involved in Gdf5 expression by performing two-step screening. We first performed microarray analyses to find transcription factors spe
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