# DMP1-Mediated FAK Activation Contributes to P Utilization of Broiler Osteoblasts by Suppressing FGF23 Expression

## TL;DR

This study shows how DMP1 helps broiler osteoblasts use phosphorus more efficiently by suppressing FGF23 through FAK activation.

## Contribution

The study identifies a novel DMP1-FAK-FGF23 regulatory axis in broiler osteoblasts for phosphorus utilization.

## Key findings

- DMP1 overexpression increases phosphorus utilization and mineralization in broiler osteoblasts.
- DMP1 suppresses FGF23 expression via FAK activation, enhancing P efficiency.
- Blocking FAK signaling reverses the effects of DMP1 on FGF23 and P utilization.

## Abstract

This study was conducted to explore how dentin matrix protein 1 (DMP1) promotes phosphorus (P) utilization of broiler osteoblasts. Our results reveal that suppressing fibroblast growth factor 23 (FGF23) expression is beneficial for P utilization of broiler osteoblasts. Interestingly, DMP1 inhibits FGF23 expression in broiler osteoblasts, which appears to be mediated through the focal adhesion kinase (FAK) activation. This process allows the broiler osteoblasts to use P more efficiently. Our results offer a novel insight into the functionality of DMP1, which would be useful for formulating feasible strategies and/or breeding programs to improve P utilization in poultry.

Improving phosphorus (P) utilization in broilers is crucial for reducing feed costs and environmental pollution. Bone mineralization trait is strongly associated with P utilization in poultry and is thus often used as an alternative trait for evaluating P utilization. Dentin matrix protein 1 (DMP1), an essential matrix protein for bone mineralization and P deposition, has been shown to be actively involved in P utilization in broilers, but the underlying mechanisms remain unclear. The current study aimed to investigate the possible mechanisms whereby DMP1 regulates P utilization of poultry by using gene silencing and overexpression technologies, combined with an in vitro model of primary broiler osteoblasts. The results showed that DMP1 overexpression augmented the P utilization of broiler osteoblasts, characterized by significant increases (p < 0.001) in P utilization rate, mineralization formation, alkaline phosphatase activity, and bone gla protein content. Meanwhile, DMP1 overexpression effectively (p < 0.05) activated the focal adhesion kinase (FAK) signaling, along with obvious (p < 0.01) decreases in fibroblast growth factor 23 (FGF23) expression and production. In contrast, DMP1 silencing reversed (p < 0.05) the above effects. Consistently, FAK activation promoted (p < 0.05) P utilization accompanied by remarkable (p < 0.05) decreases in FGF23 expression and production. Furthermore, gain- and loss-of-function assays demonstrated that a high level of FGF23 contributed to impaired P utilization, while a low level was beneficial. Interestingly, blocking FAK signaling not only recovered (p < 0.05) the FGF23 expression and production in DMP1 overexpressed cells but also obviously (p < 0.05) weakened their P utilization. These findings indicate that DMP1 inhibits FGF23 expression by activating FAK, thereby contributing to P utilization in broiler osteoblasts. They reveal a novel DMP1-FAK-FGF23 regulatory axis in broiler osteoblasts and provide a potential target for improving P efficiency in poultry.