Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Abstract

Parathyroid hormone (PTH) increases both the number of osteoclast in bone and the number of early hematopoietic stem cells (HSCs) in bone marrow. We previously characterized the phenotype of multiple populations of bone marrow cells with in vitro osteoclastogenic potential in mice. Here we examined whether intermittent administration of PTH influences these osteoclast progenitor (OCP) populations. C57BL/6 mice were treated with daily injections of bPTH(1-34) (80 mg/kg/day) for 7 or 14 days. We found that PTH caused a significant increase in the percentage of TN/CD115 þ CD117 high and TN/CD115 þ CD117 int cells ( p < .05) in bone marrow on day 7. In contrast, PTH decreased the absolute number of TN/CD115 þ CD117 low cells by 39% on day 7 ( p < .05). On day 14, there was no effect of PTH on osteoclast progenitor distribution in vivo. However, PTH treatment for 7 and 14 days did increase receptor activator of NF-kB ligand (RANKL)-and macrophage colony-stimulating factor (M-CSF)-stimulated in vitro osteoclastogenesis and bone resorption in TN/ CD115 þ cells. In the periphery, 14 days of treatment increased the percentage and absolute numbers of HSCs (Lin À CD117 þ Sca-1 þ ) in the spleen ( p < .05). These data correlated with an increase in the percent and absolute numbers of HSCs in bone marrow on day 14 ( p < .05). Interestingly, the effects on hematopoietic progenitors do not depend on osteoclast resorption activity. These results suggest that in vivo PTH treatment increased in vitro osteoclastogenesis and resorption without altering the number of osteoclast precursors. This implies that in vivo PTH induces sustained changes, possibly through an epigenetic mechanism, in the in vitro responsiveness of the cells to M-CSF and RANKL. ß

Proteoglycan 4, a Novel Immunomodulatory Factor, Regulates Parathyroid Hormone Actions on Hematopoietic Cells

“…PTH decreased the percentage of splenic B220 ϩ cells in Prg4 ϩ/ϩ mice, an effect that may be secondary to PTH actions supporting the expansion of HPCs in the spleen. 42 These data suggest that proteoglycan 4 restricts peripheral blood neutrophil numbers, which does not appear to be secondary to an altered frequency of marrow immature myeloid cells. Moreover, these data indicate that proteoglycan 4 supports the frequency of marrow B-lymphocytic cells.…”

Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis

“…In addition, a rare (0.1-0.3%) highly osteoclastogenic population was characterized among lymphoid negative population within immature myeloid subset, expressing a phenotype B220 -CD3 -CD11b -/lo CD115 + and the variable level of CD117 (cKit), with CD117 hi cells being the most potent in generating osteoclasts [28]. Further dissection revealed B220 -CD3 -CD11b -/lo CD115 + CD117 + CX3CR1 + cells as a common bone marrow progenitors for osteoclasts, macrophages and DCs at the single-cell clonal level, expressing, to a certain degree, other myeloid markers such as Ly6C and F4/80 [29,30]. By using different combination of surface markers, Xiao et al identified a common bone marrow progenitor for osteoclasts, DCs and macrophages, characterized as B220 -CD117 + CD115 + CD11b lo CD27 hi .…”

“…Besides the already described expression of CX3CR1 (fractalkine (CX3CL1) receptor) and CCR2 (receptor for monocyte chemotactic protein 1 (MCP-1)/CCL2) [29,33,42], OCPs also express CXCR4, a receptor for stromal cell-derived factor 1 (SDF-1/CXCL12), secreted by bone marrow stromal cells, vascular endothelium and immature osteoblasts [40,41,43]. …”

Serum Amyloid A3 Secreted by Preosteoclasts Inhibits Parathyroid Hormone-stimulated cAMP Signaling in Murine Osteoblasts

“…All antibodies were titrated for optimal dilutions. Staining of cells for cell sorting was performed by standard staining procedures (15). All staining was done on ice, and dead cells were excluded by their ability to incorporate propidium iodide.…”