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Purpose: Inflammation is involved in the pathogenesis of diabetes, however the impact of diabetes on organ-specific autoimmune diseases remains unexplored. Experimental autoimmune uveoretinitis (EAU) is a widely accepted animal model of human endogenous uveitis. In this study, we investigated the effects of diabetic conditions on the development of EAU using a mouse diabetes model., Methods: EAU was induced in wild-type C57BL/6 (WT) mice and Ins2 Akita (Akita) mice with spontaneous diabetes by immunization with IRBP peptide. Clinical and histopathological examinations, and analysis of T cell activation state were conducted. In addition, alternations in the composition of immune cell types and gene expression profiles of relevant immune functions were identified using single-cell RNA sequencing., Results: The development of EAU was significantly attenuated in immunized Akita (Akita-EAU) mice compared with immunized WT (WT-EAU) mice, although T cells were fully activated in Akita-EAU mice, and the differentiation into Th17 cells and regulatory T (Treg) cells was promoted. However, Th1 cell differentiation was inhibited in Akita-EAU mice, and single-cell analysis indicated that gene expression associated AP-1 signaling pathway (JUN, FOS, and FOSB) was downregulated not only in Th1 cells but also in Th17, and Treg cells in Akita-EAU mice at the onset of EAU., Conclusions: In diabetic mice, EAU was significantly attenuated. This was related to selective inhibition of Th1 cell differentiation and downregulated AP-1 signaling pathway in both Th1 and Th17 cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Takeuchi, Nishio, Someya, Sato, Yoshimura, Ito and Harimoto.)

The organic matrix of nacre has been reported for its effect on osteogenesis. It was found that PFMG4 (Pinctada fucata mantle gene 4) with an N-terminal signal peptide could be secreted into nacre of Pinctada fucata (P. fucata). Here, we report that PFMG4 is highly expressed in mantle tissue and has high homology with C1q protein in different species. In MC3T3-E1 osteoblast cells, we found that highly expressed PFMG4 could suppress cell proliferation and type I collagen expression, but it could increase alkaline phosphatase activity and mineralized deposition. These results show that PFMG4 has potential ability in enhancing osteoblast differentiation, suggesting a new idea in developing medicine for the therapy of osteoporosis.

The donor-dependent supply of platelets is frequently insufficient to meet transfusion needs. To address this issue, we developed a clinically applicable strategy for the derivation of functional platelets from human pluripotent stem cells (PSCs). This approach involves the establishment of stable immortalized megakaryocyte progenitor cell lines (imMKCLs) from PSC-derived hematopoietic progenitors through the overexpression of BMI1 and BCL-XL to respectively suppress senescence and apoptosis and the constrained overexpression of c-MYC to promote proliferation. The resulting imMKCLs can be expanded in culture over extended periods (4-5 months), even after cryopreservation. Halting the overexpression of c-MYC, BMI1, and BCL-XL in growing imMKCLs led to the production of CD42b(+) platelets with functionality comparable to that of native platelets on the basis of a range of assays in vitro and in vivo. The combination of robust expansion capacity and efficient platelet production means that appropriately selected imMKCL clones represent a potentially inexhaustible source of hPSC-derived platelets for clinical application., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The spermatogenesis associated 4 gene (Spata4, previously named TSARG2) was demonstrated to participate in spermatogenesis. Here we report that Spata4 is expressed in osteoblasts and that overexpression of Spata4 accelerates osteoblast differentiation and mineralization in MC3T3-E1 cells. We found that Spata4 interacts with p-Erk1/2 in the cytoplasm and that overexpression of Spata4 enhances the phosphorylation of Erk1/2. Intriguingly, we observed that Spata4 increases the transcriptional activity of Runx2, a critical transcription factor regulating osteoblast differentiation. We showed that Spata4-activated Runx2 is through the activation of Erk1/2. Consistent with this observation, we found that overexpression of Spata4 increases the expression of osteoblastic marker genes, including osteocalcin (Ocn), Bmp2, osteopontin (Opn), type 1 collagen, osterix (Osx), and Runx2. We concluded that Spata4 promotes osteoblast differentiation and mineralization through the Erk-activated Runx2 pathway. Our findings provided new evidence that Spata4 plays a role in regulation of osteoblast differentiation., (Copyright © 2011 American Society for Bone and Mineral Research.)

Biglycan (Bgn) is a member of the small leucine-rich proteoglycan (SLRP) family found in bone extracellular matrix (ECM), and hence involved in regulating bone formation and matrix mineralization. It has been reported that Bgn facilitates osteoblast differentiation, and extracellular signal-regulated kinase (Erk) and Smad are two important pathways in regulating osteoblast differentiation. However, the underlying mechanism for Bgn facilitating osteoblast differentiation has not been fully elucidated. The present study demonstrated that the matrix protein Bgn activates Erk signaling pathway and therefore increases Runx2 transcriptional activity, in which glycosaminoglycans (GAGs) chains play an essential role. Additionally, Bgn also activated Smad pathway, another signaling pathway related with osteoblast differentiation. The activation of these two signaling pathways induced by Bgn facilitated the mineralization deposition in vitro. These results demonstrated the mechanism of Bgn promoting osteoblast differentiation and matrix mineralization.