Cyclopamine targeting hedgehog modulates nuclear control of the osteoblast activity

Author(s)

Fernandes, Celio J. da Costa ; Ferreira, Marcel Rodrigues ; Zambuzzi, Willian Fernando

• Document type: Journal article
• Source: CELLS & DEVELOPMENT; v. 174, p. 7-pg., 2023-04-07.

Abstract

It is known that cellular events underlying the processes of bone maintenance, remodeling, and repair have their basis in the embryonic production of bone. Shh signaling is widely described developing important morphoge-netic control in bone by modifying the activity of osteoblast. Furthermore, identifying whether it is associated with the modulation of nuclear control is very important to be the basis for further applications. Experimentally, osteoblasts were exposed with cyclopamine (CICLOP) considering up to 1 day and 7 days, here considered an acute and chronic responses respectively. Firstly, we have validated the osteogenic model in vitro by exposing the osteoblasts to classical differentiating solution up to 7 days to allow the analysis of alkaline phosphatase and mineralization. Conversely, our data shows that differentiating osteoblasts present higher activity of inflammasome-related genes, while Shh signaling members were lower, suggesting a negative feedback between them. Thereafter, to better know about the role of Shh signaling on this manner, functional assays using CICLOP (5 mu M) were performed and the data validates the previously hypothesis that Shh represses inflammasome related genes activities. Altogether, our data supports the anti-inflammatory effect of Shh signaling by sup-pressing Tnf alpha, Tgf beta and inflammasome related genes during osteoblast differentiation, and this comprehension might support the understanding the molecular and cellular mechanisms related in bone regeneration by reporting molecular-related osteoblast differentiation. (AU)

• FAPESP's process: 14/22689-3 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration
• Grantee: Willian Fernando Zambuzzi
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/08888-9 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration
• Grantee: Célio Junior da Costa Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/21807-6 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration
• Grantee: Célio Junior da Costa Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)