The differentiation of hematopoietic cells from hematopoietic stem cells (HSCs) in the bone marrow is dependent upon the surrounding microenvironment, or niche. Cells of the osteoblast lineage are an important component of bone marrow hematopoietic niches. We have found that signaling downstream of the parathyroid hormone receptor PPR in osteoblast progenitors is critical for B cell development.

Osteoporosis is one of the most common degenerative diseases of aging. Bone-forming osteoblasts are derived from mesenchymal stem/progenitor cells, and we are interested in the pathways that guide the commitment of mesenchymal progenitor cells into osteoblasts rather than fat-laden adipocytes.

An unlimited source of bone-forming osteoblasts would have exciting implications for regenerative medicine, disease modeling and drug screening. We are working on protocols to differentiate osteoblasts from pluripotent stem cells.

The skeleton is one of the most common sites of metastatic spread for many common cancers. In addition, many cancer patients are at the risk for bone loss due to chemotherapy and hormonal deprivation. We have found that recombinant PTH decreases breast cancer metastases to bone and are working to understand the mechanisms.

Since osteoblasts play a supporting role in the differentiation of hematopoietic cells, diseases and medications that target osteoblasts may impact hematopoiesis. We have shown that teriparatide can increase circulating hematopoietic stem cells in women with osteoporosis.

We have found that in older men, rapid bone loss is associated with changes in blood counts and especially anemia. We have also shown that anemia is associated with an increased risk of fractures.