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Perivascular osteoprogenitors are associated with trans-cortical channels of long bones.

07:00 EST 13th February 2020 | BioPortfolio

Summary of "Perivascular osteoprogenitors are associated with trans-cortical channels of long bones."

Bone remodeling and regeneration are dependent on resident stem/progenitor cells with the capability to replenish mature osteoblasts and repair the skeleton. Using lineage tracing approaches, we identified a population of Dmp1+ cells that reside within cortical bone and are distinct from osteocytes. Our aims were to characterize this stromal population of transcortical perivascular cells (TPCs) in their resident niche and evaluate their osteogenic potential. To distinguish this population from osteoblasts/osteocytes, we crossed mice containing inducible DMP1CreERT2/Ai9 tomato reporter (iDMP/T) with Col2.3GFP reporter (ColGFP), a marker of osteoblasts and osteocytes. We observed iDMP/T+;ColGFP- TPCs within cortical bone following tamoxifen injection. These cells were perivascular and located within trans-cortical channels. Ex vivo bone outgrowth cultures showed TPCs migrated out of the channels onto the plate and expressed stem cell markers such as Sca1, PDGFRβ and leptin receptor. In a cortical bone transplantation model, TPCs migrate from their vascular niche within cortical bone, and contribute to new osteoblast formation and bone tube closure. Treatment with intermittent parathyroid hormone increased TPC number and differentiation. TPCs were unable to differentiated into adipocytes in the presence of rosiglitazone in vitro or in vivo. Altogether, we have identified and characterized a novel stromal lineage-restricted osteoprogenitor that is associated with trans-cortical vessels of long bones. Functionally, we have demonstrated that this population can migrate out of cortical bone channels, expand and differentiate into osteoblasts, therefore serving as a source of progenitors contributing to new bone formation. © AlphaMed Press 2020 SIGNIFICANCE
STATEMENT:
We identified a novel population of osteoprogenitors that reside in transcortical channels and are perivascular, hereafter termed transcortical perivascular cells (TPCs). While mesenchymal stem cells and osteoprogenitors have been associated with vasculature within bone marrow; this is the first report of an osteoprogenitor specific to cortical bone that may serve as a source of osteoblasts for intracortical remodeling. To specifically examine TPCs from cortical bone, we developed a novel ex vivo cortical bone transplantation model, in which we observed that cells within cortical bone migrate out of the transplant and begin to reconstitute the bone marrow cavity and form new bone.

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Name: Stem cells (Dayton, Ohio)
ISSN: 1549-4918
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