Osteogenesis and angiogenesis are two closely correlated processes during bone growth, development, remodelling and repair. Vascular endothelial growth factor (VEGF) is an essential mediator during the process of angiogenesis. Based on an extensive literature search, which was carried out using the PubMed database and the keywords of osteogenesis, VEGF, endochondral ossification and intramembranous ossification, this manuscript reviews the role of VEGF in ossification, with emphasis on its effect in endochondral and intramembranous ossification. Osteogenesis and angiogenesis are closely correlated processes. VEGF acts as an essential mediator during these processes. It not only functions in bone angiogenesis but also in various aspects of bone development.

VEGF promotes bone remodeling by direct effects on osteoblastic cells via regulating gene expression of ALP, OCN, and OPG through VEGFR2 signaling pathway.

Chronic inflammation is a key driver for colitis-associated colorectal cancer. 5-hydroxytryptamine (5-HT), a neurotransmitter, has been reported to promote inflammation in the gastrointestinal tract. However, the mechanism behind this remains unclear. In this study, we found that 5-HT levels, as well as the expression of tryptophan hydroxylase 1 (TPH1), the 5-HT biosynthesis rate-limiting enzyme, were significantly upregulated in colorectal tumor tissues from patients with colorectal cancer, colorectal cancer mouse models, and colorectal cancer cell lines when compared with normal colorectal tissues or epithelial cell lines. Colorectal cancer cell–originated 5-HT enhanced NLRP3 inflammasome activation in THP-1 cells and immortalized bone marrow–derived macrophages (iBMDM) via its ion channel receptor, HTR3A. Mechanistically, HTR3A activation led to Ca2+ influx, followed by CaMKIIα phosphorylation (Thr286) and activation, which then induced NLRP3 phosphorylation at Ser198 (mouse: Ser194) and inflammasome assembling. The NLRP3 inflammasome mediated IL1β maturation, and release upregulated 5-HT biosynthesis in colorectal cancer cells by inducing TPH1 transcription, revealing a positive feedback loop between 5-HT and NLRP3 signaling. Silencing TPH1 or HTR3A by short hairpin RNA slowed down tumor growth in an established CT26 and iBMDM coimplanted subcutaneous allograft colorectal cancer mouse model, whereas treatment with TPH1 inhibitor 4-chloro-DL-phenylalanine or HTR3A antagonist tropisetron alleviated tumor progression in an azoxymethane/dextran sodium sulfate–induced colorectal cancer mouse model. Addressing the positive feedback loop between 5-HT and NLRP3 signaling could provide potential therapeutic targets for colorectal cancer.

Supramolecular nanomedicines based on self‐assembly of D‐peptides have been of great interest as potential candidates for cancer therapy. Neuropilin‐1 (NRP1) and mouse double minute 2 (MDM2) have been considered as the anticancer targets because of their overexpression in cancers. However, NRP1/MDM2‐targeted D‐peptide supramolecular nanomedicines remain unreported. Here, a potent anticancer D‐peptide supramolecular nanomedicine targeting NRP1 and MDM2, termed as NMTP‐5, is identified by using structure‐based virtual screening techniques. NMTP‐5 exhibits good biostability and strong cellular uptake performance. Moreover, NMTP‐5 displays strong anticancer activity to SK‐Hep‐1 cells in vitro and in vivo, with no apparent host toxicity. This work demonstrates that NMTP‐5 can be used as a potential chemotherapeutic agent for the treatment of liver cancer.