DIFFERENTIAL-EFFECTS OF WARFARIN ON MESSENGER-RNA LEVELS OF DEVELOPMENTALLY-REGULATED VITAMIN-K-DEPENDENT PROTEINS, OSTEOCALCIN, AND MATRIX CLA PROTEIN IN-VITRO

被引:21
作者
BARONE, LM
ARONOW, MA
TASSINARI, MS
CONLON, D
CANALIS, E
STEIN, GS
LIAN, JB
机构
[1] UNIV MASSACHUSETTS,MED CTR,DEPT CELL BIOL,WORCESTER,MA 01655
[2] UNIV MASSACHUSETTS,MED CTR,CTR COMPREHENS CANC,WORCESTER,MA 01655
[3] ST FRANCIS HOSP & MED CTR,DEPT MED,HARTFORD,CT 06105
[4] UNIV CONNECTICUT,SCH MED,FARMINGTON,CT 06073
关键词
D O I
10.1002/jcp.1041600207
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The role of the vitamin K dependent proteins, osteocalcin which is bone specific and matrix Gla protein (MGP) found in many tissues, has been studied by inhibition of synthesis of their characteristic amino acid, gamma-carboxyglutamic acid (Gla) with the anticoagulant sodium warfarin. The effect of sodium warfarin on expression of these proteins, and other phenotypic markers of bone and cartilage during cellular differentiation and development of tissue extracellular matrix, was examined in several model systems. Parameters assayed include cell growth (reflected by histone gene expression) and collagen types I and II, osteopontin, alkaline phosphatase, and mineralization. Studies were carried out in calvarial bone organ cultures, normal diploid rat osteoblast and chondrocyte cultures, and rat osteosarcoma cell lines ROS 17/2.8 and 25/1. In normal diploid cells, warfarin consistently stimulated cell proliferation (twofold). In osteoblast cultures, MGP mRNA levels were generally increased (three to tenfold). Notably, MGP mRNA levels were not affected in chondrocyte cultures, either with chronic or acute warfarin treatments. Osteocalcin mRNA levels and synthesis were decreased up to 50% in ROS 17/2.8 cells and in chronically treated (1 and 5 mu g/ml sodium warfarin) rat osteoblast cultures after 22 days. Early stages of osteoblast phenotype development from the proliferation period to initial tissue formation (nodules) appeared unaffected; while after day 14, further growth and mineralization of the nodule areas were significantly decreased in warfarin-treated cultures. In summary, warfarin has opposing effects on the expression of two vitamin K dependent proteins, MGP and osteocalcin, in osteoblast cultures and MGP is regulated differently between cartilage and bone as reflected by cellular mRNA levels. Additionally, warfarin effects expression of nonvitamin K dependent proteins which may reflect the influence of warfarin on endoplasmic reticulum associated enzymes. (C) 1994 Wiley-Liss, Inc.
引用
收藏
页码:255 / 264
页数:10
相关论文
共 61 条
[1]   FACTORS THAT PROMOTE PROGRESSIVE DEVELOPMENT OF THE OSTEOBLAST PHENOTYPE IN CULTURED FETAL-RAT CALVARIA CELLS [J].
ARONOW, MA ;
GERSTENFELD, LC ;
OWEN, TA ;
TASSINARI, MS ;
STEIN, GS ;
LIAN, JB .
JOURNAL OF CELLULAR PHYSIOLOGY, 1990, 143 (02) :213-221
[2]   DEVELOPMENTAL EXPRESSION AND HORMONAL-REGULATION OF THE RAT MATRIX GLA PROTEIN (MGP) GENE IN CHONDROGENESIS AND OSTEOGENESIS [J].
BARONE, LM ;
OWEN, TA ;
TASSINARI, MS ;
BORTELL, R ;
STEIN, GS ;
LIAN, JB .
JOURNAL OF CELLULAR BIOCHEMISTRY, 1991, 46 (04) :351-365
[3]  
BIENKOWSKI RS, 1978, J BIOL CHEM, V253, P4356
[4]   CIRCULATING VITAMIN-K LEVELS IN PATIENTS WITH FRACTURES [J].
BITENSKY, L ;
HART, JP ;
CATTERALL, A ;
HODGES, SJ ;
PILKINGTON, MJ ;
CHAYEN, J .
JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME, 1988, 70 (04) :663-664
[5]   DIFFERENTIAL EXPRESSION OF PHENOTYPE BY RESTING ZONE AND GROWTH REGION COSTOCHONDRAL CHONDROCYTES INVITRO [J].
BOYAN, BD ;
SCHWARTZ, Z ;
SWAIN, LD ;
CARNES, DL ;
ZISLIS, T .
BONE, 1988, 9 (03) :185-194
[6]   HORMONAL-CONTROL OF BONE COLLAGEN-SYNTHESIS INVITRO - EFFECTS OF INSULIN AND GLUCAGON [J].
CANALIS, EM ;
DIETRICH, JW ;
MAINA, DM ;
RAISZ, LG .
ENDOCRINOLOGY, 1977, 100 (03) :668-674
[7]   ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].
CHIRGWIN, JM ;
PRZYBYLA, AE ;
MACDONALD, RJ ;
RUTTER, WJ .
BIOCHEMISTRY, 1979, 18 (24) :5294-5299
[8]   BIOCHEMICAL MARKERS OF BONE TURNOVER - METHODOLOGY AND CLINICAL USE IN OSTEOPOROSIS [J].
DELMAS, PD .
AMERICAN JOURNAL OF MEDICINE, 1991, 91 :S59-S63
[9]  
DIEGELMANN RF, 1973, J BIOL CHEM, V248, P6514
[10]   EFFECTS ON FRACTURE-HEALING OF AN ANTAGONIST OF THE VITAMIN-K CYCLE [J].
DODDS, RA ;
CATTERALL, A ;
BITENSKY, L ;
CHAYEN, J .
CALCIFIED TISSUE INTERNATIONAL, 1984, 36 (02) :233-238