Ovariectomy decreases the mRNA levels of transforming growth factor-beta 1 and increases the mRNA levels of osteocalcin in rat bone in vivo.
Estrogen depletion causes postmenopausal osteoporosis. Here we report that steady state mRNA levels of transforming growth factor-beta 1 (TGF-beta 1) and osteocalcin in bone persistently decreased and increased, respectively, in vivo in estrogen-depleted rats after ovariectomy (OVX). 21 female Wistar rats (7-month-old) were randomized and underwent OVX or sham-operation, total RNA was extracted from tibiae and assessed by Northern blot analysis. OVX induced 70-80% decrease in TGF-beta 1 mRNA levels and 2- to 3-fold increase in mRNA levels of osteocalcin compared with controls three weeks after surgery. These changes persisted up to twelve weeks post-operation. OVX caused 15% reduction in femoral bone mineral density and 2-fold elevation in serum osteocalcin levels as early as two weeks post-operation. Moreover, estrogen depletion resulted in marked decrease and increase, respectively, in steady state mRNA levels of TGF-beta 1 and osteocalcin in vitro in osteoblastic rat osteosarcoma cells, ROS 17/2.8. Our results provide the first in vivo evidence that expression of TGF-beta and osteocalcin in bone is reciprocally regulated at the transcriptional level in estrogen deficient OVX rats and suggests that TGF-beta 1 may play a role in estrogen-dependent maintenance of normal bone density.
Ikeda
T
T
Department of Orthopaedic Surgery, Kyoto University Faculty of Medicine, Japan.
Shigeno
C
C
Kasai
R
R
Kohno
H
H
Ohta
S
S
Okumura
H
H
Konishi
J
J
Yamamuro
T
T
D000591:Amino Acid Isomerases / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015519:Bone Density; D001862:Bone Resorption / Q000209:etiology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005786:Gene Expression Regulation; D015675:Osteocalcin / Q000096:biosynthesis* / Q000235:genetics; D010010:Osteoclasts / Q000378:metabolism; D010052:Ovariectomy; D019696:Peptidylprolyl Isomerase; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D002352:Carrier Proteins; D004967:Estrogens; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase