title: 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 µg/kg/day) for 7 or 14 days. We found that PTH caused a significant increase in the percentage of TN/CD115(+) CD117(high) and TN/CD115(+) CD117(int) cells (p < .05) in bone marrow on day 7. In contrast, PTH decreased the absolute number of TN/CD115(+) 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-κB ligand (RANKL)- and macrophage colony-stimulating factor (M-CSF)-stimulated in vitro osteoclastogenesis and bone resorption in TN/CD115(+) cells. In the periphery, 14 days of treatment increased the percentage and absolute numbers of HSCs (Lin(-) CD117(+) Sca-1(+) ) 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.
authors: Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Christian E
authors: CE
authors: Jacome-Galarza
authors: Sun-Kyeong
authors: SK
authors: Lee
authors: Joseph A
authors: JA
authors: Lorenzo
authors: Hector Leonardo
authors: HL
authors: Aguila
references: Nature. 2003 Oct 23;425(6960):841-6
references: 14574413
references: N Engl J Med. 2001 May 10;344(19):1434-41
references: 11346808
references: Science. 1973 May 25;180(4088):875
references: 4706681
references: Annu Rev Immunol. 2007;25:51-69
references: 17042735
references: J Bone Miner Res. 1999 Sep;14(9):1504-12
references: 10469278
references: Bone. 2009 Feb;44(2):275-86
references: 19010455
references: Nat Biotechnol. 2007 Feb;25(2):238-43
references: 17237769
references: Endocr Rev. 2008 Jun;29(4):403-40
references: 18451259
references: Science. 1988 Jul 1;241(4861):58-62
references: 2898810
references: J Bone Miner Res. 2009 Feb;24(2):209-20
references: 18847326
references: J Bone Miner Res. 2005 Jan;20(1):5-14
references: 15619664
references: Science. 2000 Sep 1;289(5484):1508-14
references: 10968781
references: J Bone Miner Res. 2009 Sep;24(9):1586-97
references: 19419301
references: Bone. 2008 Apr;42(4):806-18
references: 18234576
references: Osteoporos Int. 2010 Oct;21(10):1741-50
references: 19949772
references: Science. 1991 Nov 15;254(5034):1024-6
references: 1658941
references: Bone. 2003 Sep;33(3):372-9
references: 13678779
references: Eur J Endocrinol. 2010 May;162(5):979-86
references: 20156969
references: Endocrinology. 1999 Aug;140(8):3552-61
references: 10433211
references: J Exp Med. 1992 Jan 1;175(1):175-84
references: 1346154
references: Cell. 1997 Nov 28;91(5):661-72
references: 9393859
references: Nat Med. 2007 Jul;13(7):791-801
references: 17618270
references: Nature. 2003 Oct 23;425(6960):836-41
references: 14574412
references: Exp Hematol. 2008 Sep;36(9):1157-66
references: 18504066
references: Pediatrics. 2007 Mar;119 Suppl 2:S150-62
references: 17332236
references: Clin Chem. 1999 Aug;45(8 Pt 2):1353-8
references: 10430818
references: Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14541-6
references: 11724967
references: Endocrinology. 2005 Nov;146(11):4584-96
references: 16081645
references: J Endocrinol. 1998 Sep;158(3):341-50
references: 9846163
references: Science. 2000 Sep 1;289(5484):1504-8
references: 10968780
references: J Biol Chem. 2007 Nov 9;282(45):33086-97
references: 17690103
references: J Bone Miner Res. 2006 Jan;21(1):67-77
references: 16355275
references: Bone. 1997 Apr;20(4):335-40
references: 9108353
references: Bone. 2000 Oct;27(4):471-8
references: 11033441
references: Endocr Rev. 1999 Jun;20(3):345-57
references: 10368775
references: J Clin Invest. 1999 Feb;103(4):517-24
references: 10021460
references: J Bone Miner Res. 1998 Apr;13(4):581-9
references: 9556058
references: Nature. 2009 Jan 1;457(7225):92-6
references: 19052546