Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells

Laura M. Calvi, Olga Bromberg, Yumie Rhee, Jonathan M. Weber, Julianne N.P. Smith, Miles J. Basil, Benjamin J. Frisch, Teresita Bellido

Research output: Contribution to journalArticle

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Abstract

Microenvironmental expansion of hematopoietic stem cells (HSCs) is induced by treatment with parathyroid hormone (PTH) or activation of the PTH receptor (PTH1R) in osteoblastic cells; however, the osteoblastic subset mediating this action of PTH is unknown. Osteocytes are terminally differentiated osteoblasts embedded in mineralized bone matrix but are connected with the BM. Activation of PTH1R in osteocytes increases osteoblastic number and bone mass. To establish whether osteocyte-mediated PTH1R signaling expands HSCs, we studied mice expressing a constitutively active PTH1R in osteocytes (TG mice). Osteoblasts, osteoclasts, and trabecular bone were increased in TG mice without changes in BM phenotypic HSCs or HSC function. TG mice had progressively increased trabecular bone but decreased HSC function. In severely affected TG mice, phenotypic HSCs were decreased in the BM but increased in the spleen. TG osteocytes had no increase in signals associated with microenvironmental HSC support, and the spindle-shaped osteoblastic cells that increased with PTH treatment were not present in TG bones. These findings demonstrate that activation of PTH1R signaling in osteocytes does not expand BM HSCs, which are instead decreased in TG mice. Therefore, osteocytes do not mediate the HSC expansion induced by PTH1R signaling. Further, osteoblastic expansion is not sufficient to increase HSCs.

Original languageEnglish (US)
Pages (from-to)2489-2499
Number of pages11
JournalBlood
Volume119
Issue number11
DOIs
StatePublished - Mar 15 2012

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Parathyroid Hormone Receptor Type 1
Osteocytes
Hematopoietic Stem Cells
Stem cells
Bone
Parathyroid Hormone
Chemical activation
Osteoblasts
Bone and Bones
Bone Matrix
Osteoclasts
Spleen

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells. / Calvi, Laura M.; Bromberg, Olga; Rhee, Yumie; Weber, Jonathan M.; Smith, Julianne N.P.; Basil, Miles J.; Frisch, Benjamin J.; Bellido, Teresita.

In: Blood, Vol. 119, No. 11, 15.03.2012, p. 2489-2499.

Research output: Contribution to journalArticle

Calvi, Laura M. ; Bromberg, Olga ; Rhee, Yumie ; Weber, Jonathan M. ; Smith, Julianne N.P. ; Basil, Miles J. ; Frisch, Benjamin J. ; Bellido, Teresita. / Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells. In: Blood. 2012 ; Vol. 119, No. 11. pp. 2489-2499.
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