Abstract
Our preliminary findings have lead us to propose bone marrow adipocyte secretions as new contributors to bone loss. Indeed, using a coculture model based on human bone marrow stromal cells, we previously showed that soluble factors secreted by adipocytes induced the conversion of osteoblasts towards an adipocyte-like phenotype. In this study, microarray gene expression profiling showed profound transcriptomic changes in osteoblasts following coculture and confirmed the enrichment of the adipocyte gene signature. Double immunofluorescence microscopic analyses demonstrated the coexpression of adipogenic and osteoblastic specific markers in individual cells, providing evidence for a transdifferentiation event. At the molecular level, this conversion was associated with upregulated expression levels of reprogramming genes and a decrease in the DNA methylation level. In line with these in vitro results, preliminary immunohistochemical analysis of bone sections revealed adipogenic marker expression in osteoblasts from elderly subjects. Altogether, these data suggest that osteoblast transdifferentiation could contribute to decreased bone mass upon ageing.
Highlights
Bone marrow stromal cells (BMSCs) are progenitor cells that can self-renew and have multipotent differentiation potential and the ability to home into tissues, possessing great potential for the repair and regeneration of damaged tissues, such as cartilage and bone [1,2,3,4]
PPARG and HSD11B1 mRNA levels were determined at various early time points during adipogenic differentiation. This enabled us to show that adipocyte-specific gene expression levels in cocultured osteoblasts (OB-CC) were comparable to those found in adipocytes precociously differentiated (Fig 1B)
Osteoblasts and adipocytes are derived from the same multipotent precursor, BMSCs [6, 27], and it has been suggested that the excessive accumulation of marrow adipocytes is caused by preferential differentiation of BMSCs into adipocytes at the expense of osteoblasts [28, 29]
Summary
Bone marrow stromal cells (BMSCs) are progenitor cells that can self-renew and have multipotent differentiation potential and the ability to home into tissues, possessing great potential for the repair and regeneration of damaged tissues, such as cartilage and bone [1,2,3,4]. Human study of osteoblast transdifferentiation but did not have a role in the decision to publish the manuscript
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