Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

Harada, S., Hiromori, Y., Nakamura, S. et al. Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds. Sci Rep 5, 8520 (2015). https://doi.org/10.1038/srep08520

Efficacy of i-Scan Imaging for the Detection and Diagnosis of Early Gastric Carcinomas

We determined comparative efficacy of i-Scan for detection and diagnosis of gastric cancer. Ten patients diagnosed with early gastric cancer based on histopathological findings were analyzed. White light and i-Scan moving images recorded from these patients in twin mode were separated into white light and i-Scan. Twelve endoscopists (three different skill levels) blinded to patient information evaluated the images. Correlation between demarcation accuracy and lesion brightness on still images was investigated. No significant differences were found in diagnostic accuracy between white light and i-Scan moving images for tumor detection rate (91.7% versus 90.8%, P = 0.777). Diagnostic accuracy of tumor size was comparable between novice and experienced endoscopists for i-Scan moving images (65.7% versus 71.1%, P = 0.528), whereas it was significantly lower for white light moving images (41.2% versus 79.5%, P = 0.019). Tumor demarcation accuracy was significantly better with white light than i-Scan still images (71.0% versus 65.8%, P = 0.033). Correlations between demarcation accuracy and brightness reached highs of 0.75 for white light and 0.89 for i-Scan imaging. Efficacy of i-Scan over that of white light imaging for detecting and diagnosing gastric cancer was not shown; however, the diagnostic capability of i-Scan can be improved if imaging conditions are optimized

SLPI is a critical mediator that controls PTH-induced bone formation

Osteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.Morimoto A., Kikuta J., Nishikawa K., et al. SLPI is a critical mediator that controls PTH-induced bone formation. Nature Communications 12, 2136 (2021); https://doi.org/10.1038/s41467-021-22402-x

Osteoblast-derived vesicles induce a switch from bone-formation to bone-resorption in vivo

Bone metabolism is regulated by the cooperative activity between bone-forming osteoblasts and bone-resorbing osteoclasts. However, the mechanisms mediating the switch between the osteoblastic and osteoclastic phases have not been fully elucidated. Here, we identify a specific subset of mature osteoblast-derived extracellular vesicles that inhibit bone formation and enhance osteoclastogenesis. Intravital imaging reveals that mature osteoblasts secrete and capture extracellular vesicles, referred to as small osteoblast vesicles (SOVs). Co-culture experiments demonstrate that SOVs suppress osteoblast differentiation and enhance the expression of receptor activator of NF-κB ligand, thereby inducing osteoclast differentiation. We also elucidate that the SOV-enriched microRNA miR-143 inhibits Runt-related transcription factor 2, a master regulator of osteoblastogenesis, by targeting the mRNA expression of its dimerization partner, core-binding factor β. In summary, we identify SOVs as a mode of cell-to-cell communication, controlling the dynamic transition from bone-forming to bone-resorbing phases in vivo.Uenaka M., Yamashita E., Kikuta J., et al. Osteoblast-derived vesicles induce a switch from bone-formation to bone-resorption in vivo. Nature Communications 13, 1066 (2022); https://doi.org/10.1038/s41467-022-28673-2