Chromatin remodeling in bone organoids: from epigenetic regulation to disease modeling and therapeutic translation.

Chromatin remodeling contributes to skeletal development, tissue homeostasis, and disease by regulating nucleosome positioning, chromatin accessibility, and histone modifications. Bone organoids can partially reproduce the three-dimensional human bone microenvironment and provide new in vitro models for studying skeletal pathophysiology. This review summarizes recent progress in chromatin remodeling and bone organoid research, with a focus on the roles of switch/sucrose non-fermenting (SWI/SNF), imitation switch (ISWI), and chromodomain helicase deoxyribonucleic acid (DNA)-binding (CHD) complexes in bone organoid regulation. We also discuss the relationships between bone organoids and enhancer remodeling, DNA methylation, histone modifications, chromatin organization, and cellular metabolism. In addition, we summarize the applications of emerging technologies, including multiomics, spatial epigenomics, and live cell imaging, in bone organoid studies. The current limitations of these models are also considered. Finally, we discuss potential directions for the further development and refinement of bone organoids. We highlight their potential applications in bone disease research, drug screening, and future clinical translation within the context of chromatin remodeling.