# Chorein Regulates Key Osteoblast Genes in UMR-106 Cells

## TL;DR

This study shows that chorein, a protein linked to a rare neurological disease, affects genes related to bone cell development in osteoblast-like cells.

## Contribution

The study reveals chorein's novel role in regulating osteoblast and osteoclast-related genes in UMR-106 cells.

## Key findings

- Chorein knockdown reduced fibroblast growth factor 23 (FGF23) gene and protein expression in UMR-106 cells.
- Phex was down-regulated and Galnt3 was up-regulated in chorein-knockdown cells.
- Chorein modulates genes involved in osteoblast and osteoclast differentiation and function.

## Abstract

Chorein is an endoplasmic reticulum protein expressed in many cell types. Loss-of-function mutations of the gene encoding chorein (VPS13A) are the cause of chorea-acanthocytosis, a rare and severe neurodegenerative disease with chorea-like movements, loss of mental function, progressive muscle weakness and misshaped erythrocytes (acanthocytes). Chorein regulates diverse cellular functions including the cytoskeleton, apoptosis, Ca2+ entry, or autophagy. Since its role in bone is enigmatic, we aimed to explore the function of chorein in osteoblasts. To this end, we generated UMR-106 osteoblast-like cells with stable chorein knockdown (KD) using a CRISPR/Cas9-based approach and compared them to cells undergoing CRISPR/Cas9 with a non-targeting sequence (NT). Gene expression was assessed by qPCR and protein by Western blotting and ELISA. Gene and protein expression of chorein and fibroblast growth factor 23 (FGF23), an osteoblast-derived hormonal regulator of phosphate metabolism, were decreased in KD compared to NT cells. Moreover, FGF23 regulator Phex was down- and Galnt3 was up-regulated in KD compared to NT cells. The expression of further genes regulating osteoblast and osteoclast differentiation was affected by chorein knockdown. Taken together, chorein is expressed in UMR-106 osteoblasts and modulates the expression of various genes affecting osteoblast and osteoclast differentiation and function.

The online version contains supplementary material available at 10.1007/s12013-025-01939-4.