A Novel Role for Thrombopoietin in Regulating Osteoclast Development in Humans and Mice

被引:20
作者
Bethel, Monique [1 ]
Barnes, Calvin L. T. [2 ]
Taylor, Amanda F. [1 ]
Cheng, Ying-Hua [1 ]
Chitteti, Brahmananda R. [3 ]
Horowitz, Mark C. [2 ]
Bruzzaniti, Angela [4 ,5 ]
Srour, Edward F. [3 ,6 ,7 ]
Kacena, Melissa A. [1 ,2 ,5 ]
机构
[1] Indiana Univ Sch Med, Dept Orthopaed Surg, Indianapolis, IN 46202 USA
[2] Yale Univ, Sch Med, Dept Orthopaed & Rehabil, New Haven, CT 06510 USA
[3] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA
[4] Indiana Univ, Sch Dent, Dept Oral Biol, Indianapolis, IN USA
[5] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA
[6] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA
[7] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA
关键词
C-MPL LIGAND; BONE-MARROW; MYELOPROLIFERATIVE SYNDROME; OSTEOBLAST PROLIFERATION; MESSENGER-RNA; MEGAKARYOCYTES; EXPRESSION; RECEPTOR; LOCALIZATION; DEFICIENT;
D O I
10.1002/jcp.24943
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Emerging data suggest that megakaryocytes (MKs) play a significant role in skeletal homeostasis. Indeed, osteosclerosis observed in several MK-related disorders may be a result of increased numbers of MKs. In support of this idea, we have previously demonstrated that MKs increase osteoblast (OB) proliferation by a direct cell-cell contact mechanism and that MKs also inhibit osteoclast (OC) formation. As MKs and OCs are derived from the same hematopoietic precursor, in these osteoclastogenesis studies we examined the role of the main MK growth factor, thrombopoietin (TPO) on OC formation and bone resorption. Here we show that TPO directly increases OC formation and differentiation in vitro. Specifically, we demonstrate the TPO receptor (c-mpl or CD110) is expressed on cells of the OC lineage, c-mpl is required for TPO to enhance OC formation in vitro, and TPO activates the mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription, and nuclear factor-kappaB signaling pathways, but does not activate the PI3K/AKT pathway. Further, we found TPO enhances OC resorption in CD14+CD110+ human OC progenitors derived from peripheral blood mononuclear cells, and further separating OC progenitors based on CD110 expression enriches for mature OC development. The regulation of OCs by TPO highlights a novel therapeutic target for bone loss diseases and may be important to consider in the numerous hematologic disorders associated with alterations in TPO/c-mpl signaling as well as in patients suffering from bone disorders. J. Cell. Physiol. 230: 2142-2151, 2015. (c) 2015 Wiley Periodicals, Inc.
引用
收藏
页码:2142 / 2151
页数:10
相关论文
共 57 条
[1]
A RAPID MICROPREPARATION TECHNIQUE FOR EXTRACTION OF DNA-BINDING PROTEINS FROM LIMITING NUMBERS OF MAMMALIAN-CELLS [J].
ANDREWS, NC ;
FALLER, DV .
NUCLEIC ACIDS RESEARCH, 1991, 19 (09) :2499-2499
[2]
IDENTIFICATION AND CLONING OF A MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR THAT IS A LIGAND FOR THE CYTOKINE RECEPTOR MPL [J].
BARTLEY, TD ;
BOGENBERGER, J ;
HUNT, P ;
LI, YS ;
LU, HS ;
MARTIN, F ;
CHANG, MS ;
SAMAL, B ;
NICHOL, JL ;
SWIFT, S ;
JOHNSON, MJ ;
HSU, RY ;
PARKER, VP ;
SUGGS, S ;
SKRINE, JD ;
MEREWETHER, LA ;
CLOGSTON, C ;
HSU, E ;
HOKOM, MM ;
HORNKOHL, A ;
CHOI, E ;
PANGELINAN, M ;
SUN, Y ;
MAR, V ;
MCNINCH, J ;
SIMONET, L ;
JACOBSEN, F ;
XIE, C ;
SHUTTER, J ;
CHUTE, H ;
BASU, R ;
SELANDER, L ;
TROLLINGER, D ;
SIEU, L ;
PADILLA, D ;
TRAIL, G ;
ELLIOTT, G ;
IZUMI, R ;
COVEY, T ;
CROUSE, J ;
GARCIA, A ;
XU, W ;
DELCASTILLO, J ;
BIRON, J ;
COLE, S ;
HU, MCT ;
PACIFICI, R ;
PONTING, I ;
SARIS, C ;
WEN, D .
CELL, 1994, 77 (07) :1117-1124
[3]
Osteoclast formation and bone resorption are inhibited by megakaryocytes [J].
Beeton, C. A. ;
Bord, S. ;
Ireland, D. ;
Compston, J. E. .
BONE, 2006, 39 (05) :985-990
[4]
Megakaryocytes modulate osteoblast synthesis of type-1 collagen, osteoprotegerin, and RANKL [J].
Bord, S ;
Frith, E ;
Ireland, DC ;
Scott, MA ;
Craig, JIO ;
Compston, JE .
BONE, 2005, 36 (05) :812-819
[5]
BRETONGORIUS J, 1992, BLOOD, V79, P936
[6]
THROMBOPOIETIN (C-MPL LIGAND) ACTS SYNERGISTICALLY WITH ERYTHROPOIETIN, STEM-CELL FACTOR, AND INTERLEUKIN-11 TO ENHANCE MURINE MEGAKARYOCYTE COLONY GROWTH AND INCREASES MEGAKARYOCYTE PLOIDY IN-VITRO [J].
BROUDY, VC ;
LIN, NL ;
KAUSHANSKY, K .
BLOOD, 1995, 85 (07) :1719-1726
[7]
CarverMoore K, 1996, BLOOD, V88, P803
[8]
Stimulation of osteoprotegerin production is responsible for osteosclerosis in mice overexpressing TPO [J].
Chagraoui, C ;
Tulliez, M ;
Smayra, T ;
Komura, E ;
Giraudier, S ;
Yun, T ;
Lassau, N ;
Vainchenker, W ;
Wendling, F .
BLOOD, 2003, 101 (08) :2983-2989
[9]
Expression of osteoprotegerin mRNA and protein in murine megakaryocytes [J].
Chagraoui, H ;
Sabri, S ;
Capron, C ;
Villeval, JL ;
Vainchenker, W ;
Wendling, F .
EXPERIMENTAL HEMATOLOGY, 2003, 31 (11) :1081-1088
[10]
Pathogenesis of myelofibrosis with myeloid metaplasia: Insight from mouse models [J].
Chagraoui, Hedia ;
Wendling, Francoise ;
Vainchenker, William .
BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY, 2006, 19 (03) :399-412