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Review
. 2024 Feb 15;154(Pt C):275-285.
doi: 10.1016/j.semcdb.2022.11.002. Epub 2022 Nov 12.

Epigenetic regulation of bone remodeling and bone metastasis

Gunjan Sharma  1 , Ashrafi Sultana  1 , K M Abdullah  1 , Ramesh Pothuraju  1 , Mohd Wasim Nasser  2 , Surinder Kumar Batra  3 , Jawed Akhtar Siddiqui  4
Affiliations
Review

Epigenetic regulation of bone remodeling and bone metastasis

Gunjan Sharma et al. Semin Cell Dev Biol. .

Abstract

Bone remodeling is a continuous and dynamic process of bone formation and resorption to maintain its integrity and homeostasis. Bone marrow is a source of various cell lineages, including osteoblasts and osteoclasts, which are involved in bone formation and resorption, respectively, to maintain bone homeostasis. Epigenetics is one of the elementary regulations governing the physiology of bone remodeling. Epigenetic modifications, mainly DNA methylation, histone modifications, and non-coding RNAs, regulate stable transcriptional programs without causing specific heritable alterations. DNA methylation in CpG-rich promoters of the gene is primarily correlated with gene silencing, and histone modifications are associated with transcriptional activation/inactivation. However, non-coding RNAs regulate the metastatic potential of cancer cells to metastasize at secondary sites. Deregulated or altered epigenetic modifications are often seen in many cancers and interwound with bone-specific tropism and cancer metastasis. Histone acetyltransferases, histone deacetylase, and DNA methyltransferases are promising targets in epigenetically altered cancer. High throughput epigenome mapping and targeting specific epigenetics modifiers will be helpful in the development of personalized epi-drugs for advanced and bone metastasis cancer patients. This review aims to discuss and gather more knowledge about different epigenetic modifications in bone remodeling and metastasis. Further, it provides new approaches for targeting epigenetic changes and therapy research.

Keywords: Acetylation; And Bone metastasis; Bone remodeling; Circular RNA; DNA methylation; Epigenetic modification; Histone modifications; Long non-coding RNA; MicroRNA; Non-coding RNA.

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Conflict of interest statement

Conflict of interest SKB is a co-founder of Sanguine Diagnostics and Therapeutics, Inc. Other authors declare no competing interests.

Figures

Figure 1:
Figure 1:. Epigenetic modifications and consequences in cancer:
(A) Major lifestyle factors such as physical activity, aging, and food habits are associated with epigenetic changes in normal and cancer cells. (B) DNA methylation, histone modifications, and non-coding RNAs (micro-RNA, long non-coding RNAs, and circular RNAs) are essential mechanisms for the epigenetic reprogramming of tumor suppressors and proto-oncogenes. (C) Altered epigenetic modifications in cancer cells regulate various cellular responses, including cell proliferation, metabolism, angiogenesis, cell death, invasion, and metastasis. Most commonly, hypermethylation is associated with gene silencing, such as tumor suppressor genes and hypomethylations activate the genes, such as proto-oncogenes. However, histone modifications are associated with transcriptional activation/inactivation.
Figure 2:
Figure 2:. Epigenetic regulations in bone metastasis and remodeling.
DNA methylation maintains the OPG and RANKL proportion by hypermethylation gene silencing. Histone modifications also regulate OPG and osteoclast differentiation by the NFATC1 gene. Whereas non-coding RNAs control the expression of RUNX2 and NFATC1 genes and modulate the osteoblast and osteoclast differentiation, respectively. Additionally, DNMTs interfere with the methylation-mediated silencing of miRNAs via miR-133a-3p/MAML1/DNMT3A positive feedback loop mechanism, which potentiates cancer cells for bone metastatic niche formation through osteoblast and osteoclast differentiation. PI3K/AKT, MAPK, WNT/β-catenin, TGF-β, JAK/STAT, and mTOR are the major signaling pathways in miRNA-mediated bone metastasis and remodeling.
See this image and copyright information in PMC

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