PANoptosis in cancer, the triangle of cell death.

BACKGROUND: PANoptosis is a novel form of programmed cell death (PCD) found in 2019 that is regulated by the PANoptosome. PANoptosis combines essential features of pyroptosis, apoptosis, and necroptosis, forming a "death triangle" of cells. While apoptosis, pyroptosis, and necroptosis have been extensively studied for their roles in human inflammatory diseases and many other clinical conditions, historically they were considered as independent processes. However, emerging evidence indicates that these PCDs exhibit cross talk and interactions, resulting in the development of the concept of PANoptosis. METHODS: In this review, we offer a concise summary of the fundamental mechanisms of apoptosis, pyroptosis, and necroptosis. We subsequently introduce the notion of PANoptosis and detail the assembly mechanism of the PANoptosome complex which is responsible for inducing cell death. We also describe some regulatory networks of PANoptosis. RESULTS: PANoptosis now has been associated with various human diseases including cancer. Although the exact function of PANoptosis in each tumor is not fully understood, it represents a prospective avenue for cancer therapy, offering promise for advancements in cancer therapy. CONCLUSIONS: In the future, in-depth study of PANoptosis will continue to help us in understanding the fundamental processes underlying cell death and provide scientific support for cancer research.

Aptamer Technology and Its Applications in Bone Diseases.

Aptamers are single-stranded nucleic acids (DNA, short RNA, or other artificial molecules) produced by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology, which can be tightly and specifically combined with desired targets. As a comparable alternative to antibodies, aptamers have many advantages over traditional antibodies such as a strong chemical stability and rapid bulk production. In addition, aptamers can bind targets in various ways, and are not limited like the antigen-antibody combination. Studies have shown that aptamers have tremendous potential to diagnose and treat clinical diseases. However, only a few aptamer-based drugs have been used because of limitations of the aptamers and SELEX technology. To promote the development and applications of aptamers, we present a review of the methods optimizing the SELEX technology and modifying aptamers to boost the selection success rate and improve aptamer characteristics. In addition, we review the application of aptamers to treat bone diseases.

BMP2 induces hMSC osteogenesis and matrix remodeling.

With increasing age, the microenvironment in the bone marrow is altered, leading to a decrease in bone marrow mesenchymal stem cell (BMSC) differentiation, which reduces the number of bone cells and weakens osteogenic capacity, resulting in osteoporosis (OP). The clinical manifestations of OP include bone loss, bone microstructural destruction and altered bone quality. Bone morphogenetic protein 2 (BMP2) serves an important role in inducing the osteogenic differentiation of mesenchymal stem cells (MSCs). Regulating the bone marrow matrix microenvironment and promoting osteogenic differentiation of BMSCs is of significance for both the prevention and treatment of OP. In the present study, isobaric tags for relative and absolute quantification (iTRAQ) high­throughput proteomics technology was combined with bioinformatics analysis to screen 249 differentially expressed proteins in human MSCs overexpressing BMP2, of which 173 were upregulated and 76 proteins were downregulated. The proteins were also involved in signaling pathways associated with extracellular matrix organization, osteoblast differentiation, ossification, bone development, chondrocyte differentiation and bone morphogenesis. By carefully screening the proteins, N­cadherin (CDH2), a protein with osteogenic differentiation potential, was verified by perturbations in the background of BMP2 overexpression. The role of CDH3 in the osteogenic differentiation of MSCs was confirmed by the regulation of several cognate osteogenic markers, suggesting CDH2 as a promising candidate in the field of osteogenesis.

Overexpressing Runx2 of BMSCs Improves the Repairment of knee Cartilage Defects.

BACKGROUND: Recruitment of gene modifying bone marrow mesenchymal stem cells (BMSCs) has been considered an alternative to single-cell injection in articular cartilage repair. PURPOSE: This study aimed to investigate whether the effect of runt-related transcription factor 2(Runx2) overexpression bone marrow mesenchymal stem cells in vivo could improve the quality of repaired tissue of a knee cartilage defect in a rabbit model. METHODS: Thirty-two New Zealand rabbits were randomly divided into four groups. The blank group (Con) did not receive anything, the model group (Mo) was administered saline, the simple stem cell group (MSCs) received MSCs injection, and the Runx2 transfection group (R-MSCs) received Runx2 overexpression MSCs injection. After adapting to the environment for a week, a 5 mm diameter cylindrical osteochondral defect was created in the center of the medial femoral condyle. Cell and saline injections were performed in the first and third weeks after surgery. The cartilage repair was evaluated by macroscopically and microscopically at 4 and 8 weeks. RESULTS: Macroscopically, defects were filled and surfaces were smoother in the MSCs groups than in the Mo group at 4th week. Microscopically, the R-MSCs group showed coloration similar to surrounding normal articular cartilage tissue at 8 weeks in masson trichrome staining. The COL-II, SOX9, and Aggrecan mRNA expressions of MSCs were enhanced at 4 weeks compared with R-MSCs, then the expression reduced at 8 weeks, but was still higher than Mo group level (P<0.05). The western blot examination revealed that the COL-IIand SOX9 expression of MSCs was higher than R-MSCs at 4 weeks, then the expression reduced at 8 weeks, but was still higher than the Mo level (P<0.05). The IL-1ß content in the joint fluid also revealed that cartilage repair with R-MSCs was better than that with MSCs at 8 weeks (P<0.05). CONCLUSION: The R-MSCs group showed cellular morphology and arrangement similar to surrounding normal articular cartilage tissue, and Runx2 overexpression of MSCs resulted in overall superior cartilage repair as compared with MSCs at 8 weeks.