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Review
. 2024 Jan 27;5(2):zqae004.
doi: 10.1093/function/zqae004. eCollection 2024.

Epigenetic Regulation of Autophagy in Bone Metabolism

Affiliations
Review

Epigenetic Regulation of Autophagy in Bone Metabolism

Yazhou Zhang et al. Function (Oxf). .

Abstract

The skeletal system is crucial for supporting bodily functions, protecting vital organs, facilitating hematopoiesis, and storing essential minerals. Skeletal homeostasis, which includes aspects such as bone density, structural integrity, and regenerative processes, is essential for normal skeletal function. Autophagy, an intricate intracellular mechanism for degrading and recycling cellular components, plays a multifaceted role in bone metabolism. It involves sequestering cellular waste, damaged proteins, and organelles within autophagosomes, which are then degraded and recycled. Autophagy's impact on bone health varies depending on factors such as regulation, cell type, environmental cues, and physiological context. Despite being traditionally considered a cytoplasmic process, autophagy is subject to transcriptional and epigenetic regulation within the nucleus. However, the precise influence of epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNA expression, on cellular fate remains incompletely understood. The interplay between autophagy and epigenetic modifications adds complexity to bone cell regulation. This article provides an in-depth exploration of the intricate interplay between these two regulatory paradigms, with a focus on the epigenetic control of autophagy in bone metabolism. Such an understanding enhances our knowledge of bone metabolism-related disorders and offers insights for the development of targeted therapeutic strategies.

Keywords: autophagy; bone homeostasis; bone metabolism; bone-related diseases; epigenetics; miRNA.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Bone resorption and bone formation maintain the dynamic balance of bone homeostasis. Mesenchymal stem cells in the bone marrow gradually differentiate into osteoblasts, with key transcription factors such as BMPS, Runx2, and OSX playing critical roles in regulating osteoblast differentiation and bone matrix synthesis. Hematopoietic stem cells differentiate into mononucleated osteoclasts under the influence of M-CSF secreted by osteoblasts. Upon activation by RANKL-RANK signaling, these cells further differentiate into mononuclear resorbing cells and subsequently fuse into multinucleated osteoclasts.
Figure 2.
Figure 2.
Under the influence of genetic or pathogenic environmental conditions, histone modifications and ncRNAs promote or inhibit autophagy by targeting autophagy-related genes and proteins. Disordered autophagy leads to the occurrence and progression of bone metabolism-related diseases.
Figure 3.
Figure 3.
Epigenetic modifications regulate autophagy in bone metabolic diseases. (A) Histone modification and miRNA's inhibition of autophagy results in enhanced osteoclast generation and impedes osteoblast differentiation, causing increased bone resorption relative to bone formation, ultimately leading to osteoporosis. (B) DNA methylation modification and miRNA's inhibition of autophagy lead to increased chondrocyte apoptosis, hindered chondrocyte proliferation, and differentiation, leading to the onset of osteoarthritis. (C-F), Autophagy demonstrates a dual role in osteosarcoma. Its inhibition can either promote or impede the proliferation of osteosarcoma cells. Simultaneously, inducing autophagy can trigger cell apoptosis or elevate the survival rate of osteosarcoma cells.

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