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Effects of Ilex paraguariensis extracts on osteogenesis and bone microenvironment in mouse osteoblasts (MC3T3-E1)

ABSTRACT: Osteoporosis is a metabolic disease characterized by the destruction of bone microarchitecture and bone loss, which increases the risk of fractures and reduces quality of life. Understanding the biological mechanisms that promote bone formation is therefore of great importance. In this study, we performed transcriptomic sequencing to molecularly elucidate the effects of Ilex paraguariensis extracts on bone formation and bone-related health. Thus, this study identifies the potential mechanisms by which Ilex paraguariensis and Ligularia fischeri extracts influence bone formation and the bone microenvironment and suggests potential targets and benchmarks for biological research.

ORGANISM(S): Mus musculus

PROVIDER: GSE301490 | GEO | 2025/07/07

REPOSITORIES: GEO

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Project description:Epigenetic regulation of bone formation is a complex network of active proteins and their cofactors. Recent developments in calcified tissue research have revealed several important pathways of epigenetic regulation leading to transcriptional changes in bone cells. Rest Corepressor 2 (Rcor2) is a coregulator of Lysine-specific histone demethylase 1 (Lsd1), a demethylase linked to osteoblast activity, hematopoietic stem cell differentiation and malignancy of different neoplasms. However, the role of Rcor2 in osteoblast differentiation has not yet been examined in detail. We have previously shown that Rcor2 is highly expressed in mesenchymal stromal cells (MSC) and particularly in the osteoblastic lineage. The role of Rcor2 in osteoblastic differentiation in vitro was further characterized and we demonstrate here that lentiviral silencing of Rcor2 in MC3T3-E1 cells led to a decrease in osteoblast differentiation, as shown by decreased alkaline phosphatase and von Kossa stainings as well as by decreased expression of several osteoblast-related marker genes. RNA-sequencing of the Rcor2-downregulated MC3T3-E1 cells revealed decreased repression of Rcor2 target genes, as well as significant upregulation of majority of the differentially expressed genes. While the heterozygous, global loss of Rcor2 in vivo did not lead to a detectable bone phenotype, conditional deletion of Rcor2 in limb-bud mesenchymal cells led to a moderate decrease in cortical bone volume, which was not accentuated by challenging bone formation by ovariectomy or tibial fracture. Furthermore, a global deletion of Rcor2 led to decreased amount of white adipose tissue in vivo and decreased the capacity of primary cells to differentiate into adipocytes in vitro, while the conditional deletion led to decreased adiposity in fracture calluses. Taken together, these results suggest that epigenetic regulation of mesenchymal stromal cell differentiation is mediated by Rcor2, which could thus play an important role in defining the MSC fate.

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Effects of Ilex paraguariensis extracts on osteogenesis and bone microenvironment in mouse osteoblasts (MC3T3-E1)

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