Parathyroid hormone mediates hematopoietic cell expansion through interleukin-6.

Parathyroid hormone mediates hematopoietic cell expansion through interleukin-6.

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Parathyroid hormone (PTH) stimulates hematopoietic cells through mechanisms of action that remain elusive.Interleukin-6 (IL-6) is upregulated by PTH and stimulates hematopoiesis.The purpose of this investigation was to identify actions of PTH and IL-6 in hematopoietic cell expansion.Bone marrow cultures from C57B6 mice were treated with fms-like tyrosine kinase-3 ligand (Flt-3L), PTH, Flt-3L threadheaders.shop plus PTH, or vehicle control.

Flt-3L alone increased adherent and non-adherent cells.PTH did not directly impact hematopoietic or osteoclastic cells but acted in concert with Flt-3L to further increase cell numbers.Flt-3L alone stimulated proliferation, while PTH combined with Flt-3L decreased apoptosis.Flt-3L increased blasts early in culture, and later increased CD45(+) Air Freshener and CD11b(+) cells.

In parallel experiments, IL-6 acted additively with Flt-3L to increase cell numbers and IL-6-deficient bone marrow cultures (compared to wildtype controls) but failed to amplify in response to Flt-3L and PTH, suggesting that IL-6 mediated the PTH effect.In vivo, PTH increased Lin(-) Sca-1(+)c-Kit(+) (LSK) hematopoietic progenitor cells after PTH treatment in wildtype mice, but failed to increase LSKs in IL-6-deficient mice.In conclusion, PTH acts with Flt-3L to maintain hematopoietic cells by limiting apoptosis.IL-6 is a critical mediator of bone marrow cell expansion and is responsible for PTH actions in hematopoietic cell expansion.