Recombinant human extracellular matrix protein 1 inhibits alkaline phosphatase activity and mineralization of mouse embryonic metatarsals in vitro

被引:69
作者
Deckers, MML
Smits, P
Karperien, M
Ni, J
Tylzanowski, P
Feng, P
Parmelee, D
Zhang, J
Bouffard, E
Gentz, R
Löwik, CWG
Merregaert, J
机构
[1] Univ Instelling Antwerp, Dept Biochem, Lab Mol Biotechnol, B-2610 Wilrijk, Belgium
[2] Univ Leiden Hosp, Dept Endocrinol & Metab Dis, NL-2300 RC Leiden, Netherlands
[3] Univ Leiden Hosp, Dept Pediat, NL-2300 RC Leiden, Netherlands
[4] Human Genome Sci Inc, Rockville, MD USA
[5] Katholieke Univ Leuven, Fac Med, Lab Skeletal Dev & Joint Dis, Louvain, Belgium
关键词
Ecml; embryonic metatarsals; mineralization;
D O I
10.1016/S8756-3282(00)00428-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Two mRNAs are transcribed from the extracellular matrix protein 1 gene (Ecm1): Ecm1a and an alternatively spliced Ecm1b. We studied Ecm1 mRNA expression and localization during endochondral bone formation and investigated the effect of recombinant human (rh) Ecm1a protein on organ cultures of embryonic mouse metatarsals, Of the two transcripts, Ecm1a mRNA was predominantly expressed in fetal metacarpals from day 16 to 19 after gestation. Ecm1 expression was not found in 16- and 17-day-old metatarsals of which the perichondrium was removed. In situ hybridization and immunohistochemistry demonstrated Ecm1 expression in the connective tissues surrounding the developing bones, but not in the cartilage. Biological effects of rhEcm1a protein on fetal metatarsal cultures were biphasic: at low concentrations, Ecm1a stimulated alkaline phosphatase activity and had no effect on mineralization, whereas at higher concentrations, Ecm1a dose dependently inhibited alkaline phosphatase activity and mineralization, These results suggest that Ecm1a acts as a novel negative regulator of endochondral bone formation. (C) 2001 by Elsevier Science Inc, All rights reserved.
引用
收藏
页码:14 / 20
页数:7
相关论文
共 25 条
[1]   Programmed cell death of chondrocytes and aberrant chondrogenesis in mice homozygous for parathyroid hormone-related peptide gene deletion [J].
Amizuka, N ;
Henderson, JE ;
Hoshi, K ;
Warshawsky, H ;
Ozawa, H ;
Goltzman, D ;
Karaplis, AC .
ENDOCRINOLOGY, 1996, 137 (11) :5055-5067
[2]   A SIMPLE TECHNIQUE FOR PRESERVATION OF FIXATION-SENSITIVE ANTIGENS IN PARAFFIN-EMBEDDED TISSUES [J].
BECKSTEAD, JH .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1994, 42 (08) :1127-1134
[3]   MOLECULAR-CLONING, CHARACTERIZATION, AND GENETIC-MAPPING OF THE CDNA CODING FOR A NOVEL SECRETORY PROTEIN OF MOUSE - DEMONSTRATION OF ALTERNATIVE SPLICING IN SKIN AND CARTILAGE [J].
BHALERAO, J ;
TYLZANOWSKI, P ;
FILIE, JD ;
KOZAK, CA ;
MERREGAERT, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (27) :16385-16394
[4]  
BROWN JR, 1976, FED PROC, V35, P2141
[5]   INVITRO FORMATION OF OSTEOCLASTS FROM LONG-TERM CULTURES OF BONE-MARROW MONONUCLEAR PHAGOCYTES [J].
BURGER, EH ;
VANDERMEER, JWM ;
VANDEGEVEL, JS ;
GRIBNAU, JC ;
THESINGH, CW ;
VANFURTH, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 1982, 156 (06) :1604-1614
[6]   CHONDROCYTE DIFFERENTIATION [J].
CANCEDDA, R ;
CANCEDDA, FD ;
CASTAGNOLA, P .
INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 159, 1995, 159 :265-358
[7]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[8]   DISTINCT SPATIAL AND TEMPORAL EXPRESSION PATTERNS OF 2 TYPE-I RECEPTORS FOR BONE MORPHOGENETIC PROTEINS DURING MOUSE EMBRYOGENESIS [J].
DEWULF, N ;
VERSCHUEREN, K ;
LONNOY, O ;
MOREN, A ;
GRIMSBY, S ;
VANDESPIEGLE, K ;
MIYAZONO, K ;
HUYLEBROECK, D ;
TENDIJKE, P .
ENDOCRINOLOGY, 1995, 136 (06) :2652-2663
[9]   TOWARD A MOLECULAR UNDERSTANDING OF SKELETAL DEVELOPMENT [J].
ERLEBACHER, A ;
FILVAROFF, EH ;
GITELMAN, SE ;
DERYNCK, R .
CELL, 1995, 80 (03) :371-378
[10]   Inhibition of terminal chondrocyte differentiation by bone morphogenetic protein 7 (OP-1) in vitro depends on the periarticular region but is independent of parathyroid hormone-related peptide [J].
Haaijman, A ;
Karperien, M ;
Lanske, B ;
Hendriks, J ;
Löwik, CWGM ;
Bronckers, ALJJ ;
Burger, EH .
BONE, 1999, 25 (04) :397-404