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Abstract
Presently there is no clear evidence for the ability of mature osteogenic lineage cells to dedifferentiate. In order to identify and trace mature osteogenic lineage cells, we have utilized transgenic mouse models in which the dentin matrix protein 1 (Dmp1) promoter drives expression of GFP (active marker) or Cre recombinase (historic label) in preosteocytes/osteocytes. In long bone chip outgrowth cultures, in which cells on the bone surface were enzymatically removed, cells with previous activity of the Dmp1 promoter migrated onto plastic and down-regulated Dmp1-GFP expression. Dmp1Cre-labeled cells from these cultures had the potential to re-differentiate into the osteogenic lineage, while the negative population showed evidence of adipogenesis. We observed numerous Dmp1Cre-labeled osteoblasts on the surface of bone chips following their in vivo transplantation. Our data indicate that cells embedded in bone matrix are motile, and once given access to the extra bony milieu will migrate out of their lacunae. This population of cells is phenotypically and functionally heterogeneous in vitro. Once the preosteocytes/osteocytes leave lacunae, they can dedifferentiate, potentially providing an additional source of functional osteoblasts.
Highlights
Osteocytes, the cells residing within the bone matrix, represent more than 95% of the cellular component of adult bone tissue
Osteocytes originate from mesenchymal stem cells (MSCs) through osteoblast lineage differentiation, with only 10–20% of osteoblasts differentiating into osteocytes [1]
There are still many unanswered questions about the differentiation process, our knowledge of the transition from osteoblast to osteocyte has expanded dramatically due to the identification of several osteocyte specific markers such as dentin matrix protein 1 (Dmp1) [2,3,4,5], matrix extracellular phosphoglycoprotein (MEPE), phosphate regulating endopeptidase homolog (PHEX) and sclerostin (Sost) [6,7,8]
Summary
Osteocytes, the cells residing within the bone matrix, represent more than 95% of the cellular component of adult bone tissue. They communicate with other osteocytes, and osteoblast lineage cells at the endosteal surface through the lacuna-canalicular system. Formation of this complex network is ideally suited for mechanosensation and integration of local and systemic signals. Dmp is an extracellular matrixassociated phosphoprotein, with expression restricted to mineralized tissues in mouse, rat and chicken [2,9]. Based on the expression of Dmp in osteocytes, several investigators have utilized different lengths of the Dmp promoter to direct Cre recombination to this cell type [10,11,12,13]
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