Loss of parathyroid hormone receptor signaling in osteoprogenitors is associated with accumulation of multiple hematopoietic lineages in the bone marrow.

Osteoblasts and their progenitors play an important role in the support of hematopoiesis within the bone marrow microenvironment. We have previously reported that parathyroid hormone receptor (PTH1R) signaling in osteoprogenitors is required for normal B cell precursor differentiation, and for trafficking of maturing B cells out of the bone marrow. Cells of the osteoblast lineage have been implicated in the regulation of several other hematopoietic cell populations, but the effects of PTH1R signaling in osteoprogenitors on other maturing hematopoietic populations have not been investigated. Here we report that numbers of maturing myeloid, T cell, and erythroid populations were increased in the bone marrow of mice lacking PTH1R in osteoprogenitors (PTH1R-OsxKO mice). This increase in maturing hematopoietic populations was not associated with an increase in progenitor populations or proliferation. The spleens of PTH1R-OsxKO mice were small with decreased numbers of all hematopoietic populations, suggesting that trafficking of mature hematopoietic populations between bone marrow and spleen is impaired in the absence of PTH1R in osteoprogenitors. RNA sequencing of osteoprogenitors and their descendants in bone and bone marrow revealed increased expression of VCAM-1 and CXCL12, factors that are involved in trafficking of several hematopoietic populations.
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