The role of parathyroid hormone and insulin-like growth factors in hematopoietic niches: physiology and pharmacology.
Hematopoietic stem cells (HSC) capable of both self-renewal and differentiation into all blood lineages reside within the bone marrow in specialized microenvironmental niches. While the precise location and composition of these niches largely remains unknown, it is now believed that osteoblasts at the endosteal surface play critical roles. Among the molecules demonstrated to influence the function of these niches are parathyroid hormone (PTH) and the insulin-like growth factors (IGF). Administration of PTH to both mice and men expands the number of bone marrow HSC, and an increase in the number of those cells in peripheral blood following treatment with mobilizing agents. Several molecules downstream of PTH are capable of signaling to HSC, including IGF that appear to regulate both the survival and expansion of hematopoietic stem and progenitor cells. As our current understanding of the role for PTH and IGF in hematopoietic niches is limited, we believe it is important that both their physiological importance and pharmacological potential be more fully investigated.
Garrett
R W
RW
Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. rgarrett@mail.med.upenn.edu
Emerson
S G
SG
D000818:Animals; D006410:Hematopoiesis / Q000187:drug effects* / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010641:Phenotype; D013002:Somatomedins / Q000494:pharmacology*
D010281:Parathyroid Hormone; D013002:Somatomedins