Noggin arrests stromal cell differentiation in vitro

被引:25
作者
Gazzerro, E
Du, Z
Devlin, RD
Rydziel, S
Priest, L
Economides, A
Canalis, E
机构
[1] St Francis Hosp & Med Ctr, Dept Res, Hartford, CT 06105 USA
[2] Univ Connecticut, Sch Med, Farmington, CT USA
[3] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA
关键词
adipocytes; bone morphogenetic proteins; cytokines; glucocorticoids; growth factors; osteoblasts;
D O I
10.1016/S8756-3282(02)00948-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Noggin is a glycoprotein that binds bone morphogenetic proteins (BMPs) selectively and, when added to osteoblasts, it opposes the effects of BMPs. However, the consequences of its continued expression in stromal cells are not known. We investigated the effects of noggin overexpression under the control of a constitutive promoter, on murine ST-2 stromal cells, and its impact on stromal cells from transgenic mice overexpressing noggin under the control of the osteocalcin promoter. ST-2 cells were transduced with a retroviral vector (pLPCX) or a vector driving noggin (pLPCX noggin). Untreated (pLPCX) ST-2 cells developed the appearance of mineralized nodules and expressed osteocalcin. pLPCX noggin delayed the appearance of mineralized nodules and prevented the expression of osteocalcin. Noggin also prevented the cortisol-dependent induction of peroxisome proliferator-activated receptor gamma2 and adipsin transcripts, indicating a generalized inhibition of cell differentiation. Primary stromal cells from noggin transgenic mice displayed impaired differentiation when compared to cells from wild-type animals and did not express osteocalcin mRNA. In conclusion, noggin arrests the differentiation of stromal cells, preventing cellular maturation. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:111 / 119
页数:9
相关论文
共 52 条
[11]   The role of C/EBP genes in adipocyte differentiation [J].
Darlington, GJ ;
Ross, SE ;
MacDougald, OA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (46) :30057-30060
[12]  
DELANY AM, 1997, GROW FACT CYTOK A&B, V3, P127
[13]   Glucocorticoids inhibit bone resorption by isolated rat osteoclasts by enhancing apoptosis [J].
Dempster, DW ;
Moonga, BS ;
Stein, LS ;
Horbert, WR ;
Antakly, T .
JOURNAL OF ENDOCRINOLOGY, 1997, 154 (03) :397-406
[14]   Osf2/Cbfa1: A transcriptional activator of osteoblast differentiation [J].
Ducy, P ;
Zhang, R ;
Geoffroy, V ;
Ridall, AL ;
Karsenty, G .
CELL, 1997, 89 (05) :747-754
[15]   A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development [J].
Ducy, P ;
Starbuck, M ;
Priemel, M ;
Shen, JH ;
Pinero, G ;
Geoffroy, V ;
Amling, M ;
Karsenty, G .
GENES & DEVELOPMENT, 1999, 13 (08) :1025-1036
[16]   Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype [J].
Erlebacher, A ;
Derynck, R .
JOURNAL OF CELL BIOLOGY, 1996, 132 (1-2) :195-210
[17]   Activity of the osteocalcin promoter in skeletal sites of transgenic mice and during osteoblast differentiation in bone marrow-derived stromal cell cultures: Effects of age and sex [J].
Frenkel, B ;
Capparelli, C ;
VanAuken, M ;
Baran, D ;
Bryan, J ;
Stein, JL ;
Stein, GS ;
Lian, JB .
ENDOCRINOLOGY, 1997, 138 (05) :2109-2116
[18]   Bone morphogenetic proteins induce the expression of noggin, which limits their activity in cultured rat osteoblasts [J].
Gazzerro, E ;
Gangji, V ;
Canalis, E .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (12) :2106-2114
[19]   BONE MORPHOGENETIC PROTEINS INHIBIT ADIPOCYTE DIFFERENTIATION BY BONE-MARROW STROMAL CELLS [J].
GIMBLE, JM ;
MORGAN, C ;
KELLY, K ;
WU, X ;
DANDAPANI, V ;
WANG, CS ;
ROSEN, V .
JOURNAL OF CELLULAR BIOCHEMISTRY, 1995, 58 (03) :393-402
[20]   Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis [J].
Gong, YQ ;
Krakow, D ;
Marcelino, J ;
Wilkin, D ;
Chitayat, D ;
Babul-Hirji, R ;
Hudgins, L ;
Cremers, CW ;
Cremers, FPM ;
Brunner, HG ;
Reinker, K ;
Rimoin, DL ;
Cohn, DH ;
Goodman, FR ;
Reardon, W ;
Patton, M ;
Francomano, CA ;
Warman, ML .
NATURE GENETICS, 1999, 21 (03) :302-304