Epigenetic dynamic during endochondral ossification and articular cartilage development

Allas, Lyess; Boumédiene, Karim; Baugé, Catherine

doi:10.1016/j.bone.2018.10.004

Cited by 29 publications

(27 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, consistent with the proposed influence of hypomethylation on the activation of prochondrogenic genes (see review by ref. 22 ), the addition of 5-azacytidine to micromass cultures promoted chondrogenesis at levels similar to what was observed after Dnmt3b gene silencing ( Fig. 7j-l).…”

Section: Resultssupporting

confidence: 78%

The methylation status of the embryonic limb skeletal progenitors determines their cell fate in chicken

et al. 2020

View full text Add to dashboard Cite

Digits shape is sculpted by interdigital programmed cell death during limb development. Here, we show that DNA breakage in the periphery of 5-methylcytosine nuclei foci of interdigital precursors precedes cell death. These cells showed higher genome instability than the digit-forming precursors when exposed to X-ray irradiation or local bone morphogenetic protein (BMP) treatments. Regional but not global DNA methylation differences were found between both progenitors. DNA-Methyl-Transferases (DNMTs) including DNMT1, DNMT3B and, to a lesser extent, DNMT3A, exhibited well-defined expression patterns in regions destined to degenerate, as the interdigital tissue and the prospective joint regions. Dnmt3b functional experiments revealed an inverse regulation of cell death and cartilage differentiation, by transcriptional regulation of key genes including Sox9, Scleraxis, p21 and Bak1, via differential methylation of CpG islands across their promoters. Our findings point to a regulation of cell death versus chondrogenesis of limb skeletal precursors based on epigenetic mechanisms.

show abstract

Section: Resultssupporting

confidence: 78%

The methylation status of the embryonic limb skeletal progenitors determines their cell fate in chicken

et al. 2020

View full text Add to dashboard Cite

show abstract

“…(13) Osteoblasts (ostb) play a central role in both intramembranous ossification and in the more widespread and complicated endochondral ossification pathway for bone formation based upon chondrocytes (chond). (11) Surprisingly, there is evidence for hypertrophic chond transdifferentiating to ostb, which is consistent with the considerable overlap of transcription profiles of these two morphologically dissimilar bone cell types. (14,15) Ostb and chond are derived from a heterogeneous mixture of bone-derived stem or stem-like cells commonly referred to as mesenchymal stem cells (MSC).…”

Section: Introductionsupporting

confidence: 67%

“…All but SPECC1 have known bone-related functions. (11,18,(27)(28)(29)(30) Because we recently analyzed EnhPro SNPs for TBX15, (18) we eliminated it as well as SPECC1 from further consideration. Alternatively, we identified seven additional EnhPro SNP-associated genes, HMGA2, BMP5, DLX6, SIX1, SMAD3, TRPS1, and WNT7B, that were strongly enriched in bone biology-related Gene Ontology (GO) terms, had literature references for their skeletal association, and displayed appreciable expression in ostb, chond, or MSC (Supplemental Table S5).…”

Section: Prioritization Of 16 Snps As Candidate Causal Regulatory Snpmentioning

confidence: 99%

“…Table S6). In addition, the Alt allele of Tier-1 SNP rs2504104 overlaps predicted binding sites for RUNX2, the master regulator of ostb lineage commitment, (11) and CBFB, which can help stabilize Runx-family proteins binding to DNA (44) (Table 1). Lastly, the Alt allele of rs2504103 is predicted to bind NFIC, which plays important roles in both tooth and bone development.…”

Section: Snps For Daam2mentioning

confidence: 99%

See 1 more Smart Citation

Prioritization of osteoporosis-associated GWAS SNPs using epigenomics and transcriptomics

Zhang

Deng

Shen

et al. 2020

Preprint

View full text Add to dashboard Cite

Genetic risk factors for osteoporosis, a prevalent disease associated with aging, have been examined in many genome-wide association studies (GWAS). A major challenge is to prioritize transcription-regulatory GWAS-derived variants that are likely to be functional. Given the critical role of epigenetics in gene regulation, we have used an unusual epigenetics-and transcription-based approach to identify credible regulatory SNPs relevant to osteoporosis from 38 reported BMD GWAS. Using Roadmap databases, we prioritized SNPs based upon their overlap with strong enhancer or promoter chromatin preferentially in osteoblasts relative to 11 heterologous cell culture types. The selected SNPs also had to overlap open chromatin (DNaseI-hypersensitive sites) and DNA sequences predicted to bind to osteoblast-relevant transcription factors in an allele-specific manner. From >50,000 GWAS-derived SNPs, we identified 16 novel and credible regulatory SNPs (Tier-1 SNPs) for osteoporosis risk. Their associated genes, BICC1, LGR4, DAAM2, NPR3, or HMGA2, are involved in osteoblastogenesis or bone homeostasis and regulate cell signaling or enhancer function. Four of them are preferentially expressed in osteoblasts. BICC1, LGR4, and DAAM2 play important roles in canonical Wnt signaling, a pathway critical to bone formation and repair. The transcription factors that are predicted to bind to the Tier-1 SNP-containing DNA sequences also have bone-related functions. For the seven Tier-1 SNPs near the 5' end of BICC1, examination of eQTL overlap and the distribution of BMD-increasing alleles suggests that at least one SNP in each of two clusters contributes to inherited osteoporosis risk. Our study not only illustrates a method that can be used to identify novel BMD-related causal regulatory SNPs for future study, but also reveals evidence that some of the Tier-1 SNPs exert their effects on BMD risk indirectly through little-studied noncoding RNA genes, which in turn may control the nearby bone-related proteinencoding gene.

show abstract

“…Histone acetylation and deacetylation regulate many steps of myogenesis [47]. Histone deacetylases (HDAC) contribute to the molecular pathways and chromatin changes that regulate the tissue-specific gene expression during chondrocyte and osteoblast specification [48]. In this study, we demonstrated a morphological correlation between the muscles and bones during E15 and P0.…”

Section: Discussionmentioning

confidence: 58%

Morphological association between the muscles and bones in the craniofacial region

et al. 2020

View full text Add to dashboard Cite

The strains of inbred laboratory mice are isogenic and homogeneous for over 98.6% of their genomes. However, geometric morphometric studies have demonstrated clear differences among the skull shapes of various mice strains. The question now arises: why are skull shapes different among the mice strains? Epigenetic processes, such as morphological interaction between the muscles and bones, may cause differences in the skull shapes among various mice strains. To test these predictions, the objective of this study is to examine the morphological association between a specific part of the skull and its adjacent muscle. We examined C57BL6J, BALB/cA, and ICR mice on embryonic days (E) 12.5 and 16.5 as well as on postnatal days (P) 0, 10, and 90. As a result, we found morphological differences between C57BL6J and BALB/cA mice with respect to the inferior spine of the hypophyseal cartilage or basisphenoid (SP) and the tensor veli palatini muscle (TVP) during the prenatal and postnatal periods. There was a morphological correlation between the SP and the TVP in the C57BL6J, BALB/cA, and ICR mice during E15 and P0. However, there were not correlation between the TVP and the SP during P10. After discectomy, bone deformation was associated with a change in the shape of the adjacent muscle. Therefore, epigenetic modifications linked to the interaction between the muscles and bones might occur easily during the prenatal period, and inflammation seems to allow epigenetic modifications between the two to occur.

show abstract

Epigenetic dynamic during endochondral ossification and articular cartilage development

Cited by 29 publications

References 116 publications

The methylation status of the embryonic limb skeletal progenitors determines their cell fate in chicken

The methylation status of the embryonic limb skeletal progenitors determines their cell fate in chicken

Prioritization of osteoporosis-associated GWAS SNPs using epigenomics and transcriptomics

Morphological association between the muscles and bones in the craniofacial region

Contact Info

Product

Resources

About