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891.
Down-Regulation of Osteoblastic Cell Differentiation by Epidermal Growth Factor Receptor 总被引:6,自引:0,他引:6
The role of epidermal growth factor receptors (EGF-R) in osteogenic cell differentiation was investigated using preosteoblastic
MC3T3-E1 (MC3T3) cells and osteoblast-like ROS 17/2.8 (ROS) cells. When cultured in the presence of β-glycerophosphate (GP)
and ascorbic acid (AA), MC3T3 cells underwent spontaneous differentiation into osteoblasts which was confirmed as they expressed
osteoblast markers such as alkaline phosphatase (ALP), bone sialoprotein (BSP) and osteocalcin (OC). Interestingly, the number
of EGF-binding sites decreased during their differentiation into osteoblasts, and the osteogenic protein-1 (OP-1) treatment,
which accelerated their differentiation, lowered the number of EGF-binding sites even further. On the other hand, ROS cells
with high expression levels of osteoblast markers and no EGF-R, after being transfected with human EGF-R cDNA (EROS cells),
expressed numerous EGF-binding sites as well as EGF-R mRNA and protein; in the process, they ceased to express osteoblast
markers, indicating their dedifferentiation into osteoprogenitor cells. Both MC3T3 and EROS cells showed increased cell growth
in response to EGF, whereas ROS cells did not. These results imply that the EGF/EGF-R system in osteogenic cells has a crucial
function in osteoblast phenotype suppression and osteogenic cell proliferation. 相似文献
892.
Calcaneus Bone Mineral Density is Lower Among Men and Women with Lower Physical Performance 总被引:5,自引:0,他引:5
Aoyagi K Ross PD Hayashi T Okano K Moji K Sasayama H Yahata Y Takemoto T 《Calcified tissue international》2000,67(2):106-110
Fracture risk is influenced by both bone strength and by falls. Measures of physical function and performance are predictors
of falls. However, the interrelationships among bone mineral density (BMD), regular physical activity, and measures of physical
performance are not well known. We studied 447 community-dwelling Japanese people aged 40 years and over (96 men and 351 women)
to examine the association of calcaneus BMD with measures of physical performance (grip strength, walking speed, chair stand,
and functional reach) and regular physical activity. Calcaneus BMD decreased with age by approximately 25% in men and 42%
in women. Measures of physical performance decreased with age by approximately 30% in both genders, however, performance on
the chair stand test declined by approximately 60%. There were only minimal differences in performance measures and calcaneus
BMD between people with and those without regular physical activity in both genders, and most differences were not significant.
However, there were significant BMD increases of 3–6% per standard deviation (SD) increase in all performance measures for
women and a 7% increase in BMD per SD increase in grip strength for men, after adjusting for age. These associations remained
after additional adjustment for body mass index and regular physical activity. These findings suggest that bone density and
physical function decline markedly in both men and women with age, and that low BMD and poor function tend to occur together,
which would increase fracture risk more than either risk factor alone.
Received: 9 August 1999 / Accepted: 4 February 2000 相似文献
893.
Akhter MP Iwaniec UT Covey MA Cullen DM Kimmel DB Recker RR 《Calcified tissue international》2000,67(4):337-344
The purpose of this study was to assess breed-related differences in bone histomorphometry, bone biomechanics, and serum
biochemistry in three mouse breeds shown to differ in bone mineral density (BMD) (as measured by DXA) and bone mineral content
(BMC). Femurs, tibiae, and sera were collected from 16-week-old C3H/HeJ {C3H}, C57BL/6J {BL6}, and DBA/2J {DBA}mice (n = 12/breed).
Data collected included BMC and BMD (femora), histomorphometry of cancellous (distal femur) and cortical bone (diaphyseal
tibiae and femora), bone strength (femora), and serum alkaline phosphatase (ALP). Consistent with previous reports, BMC and
BMD were higher in C3H than in BL6 or DBA mice. The higher BMD in the C3H breed was associated with greater cancellous bone
volume, cortical bone area, periosteal bone formation rate, biomechanical strength, and serum ALP. However, mid-diaphyseal
total femoral and tibial cross-sectional area and moment of inertia were greatest in BL6, intermediate in C3H, and lowest
in DBA mice. The specific distribution of cortical bone in C3H, BL6, DBA mice represents a difference in adaptive response
to similar mechanical loads in these breeds. This difference in adaptive response may be intrinsic to the adaptive mechanism,
or may be intrinsic to the bone tissue material properties. In either case, the bone-adaptive response to ordinary mechanical
loads in the BL6 mice yields bones of lower mechanical efficiency (less stiffness per unit mass of bone tissue) and does not
adapt as well as that of the C3H mice where the final product is a bone with greater resistance to bending under load. We
suggest that the size, shape, and BMD of the bone are a result of breed-specific genetically regulated cellular mechanisms.
Compared with the C3H mice, the lower BMD in BL6 mice is associated with long bones that are weaker because the larger cross-sectional
area fails to compensate completely for their lower BMD and BMC.
Received: 16 November 1999 / Accepted: 19 April 2000 / Online publication: 27 July 2000 相似文献
894.
This study was undertaken to compare the effect of supraphysiological doses of thyroxine (T4) on bone metabolism in SHAM
and OVX young adult rats. Female Sprague Dawley rats (220 ± 2 g, approx. 5 months of age) were divided into four groups of
eight animals each. The animals were intraperitoneally injected 6 days per week with vehicle (Vh): 0.001 N NaOH/0.9% NaCl
(SHAM+Vh and OVX+Vh) or 250 μg of thyroxine/kg/day (SHAM+T4 and OVX+T4) during a 5-week period. Serum T4 and osteocalcin (BGP),
urinary pyridinolines (Pyr), and creatinine (creat) were determined. At the beginning and at end of the experiment, skeletal
bone mineral content (BMC), bone mineral density (BMD), and area (A) of the total skeleton, femur, spine, and whole tibia,
as well as proximal, middle, and distal areas of the tibia were assessed by dual X-ray absorptiometry (DXA) in an ultra-high-resolution
mode. T4 treatment of the SHAM rats did not induce significant changes in BGP level or Pyr/creat excretion compared with the
SHAM+Vh control group. However, these two biochemical bone markers significantly increased due to T4 treatment in OVX rats
compared with both OVX+Vh and SHAM+T4 groups (P < 0.05 and P < 0.001, respectively). The OVX+T4 group had a significantly lower ΔBMD than SHAM+T4 rats in all studied regions (P < 0.05) except for the middle tibia region. OVX+T4 groups presented a significantly lower ΔBMC and ΔA compared with SHAM+T4
animals (P < 0.001). OVX+T4 rats significantly impaired the ΔBMD in the femur (P < 0.01), spine (P < 0.05), whole (P < 0.05) and middle (P < 0.05) tibia whereas T4 treatment of SHAM rats only affected, significantly, the whole (P < 0.05) and the proximal tibia region (P < 0.01). T4 treatment affects bone growth in young adult rats. The effect is significantly greater in the estrogen-depleted
than in the estrogen-repleted state. The bone site most adversely affected by T4 treatment depends on the estrogen status.
The proximal tibia (principally trabecular bone) was the most affected area in estrogen-repleted rats. Conversely, in OVX
rats, the middle tibia (principally cortical bone) presented the greatest decrease in bone density.
Received: 20 May 1999 / Accepted: 4 February 2000 相似文献
895.
Our previous studies of rat cranial defect repairs after the implantation of demineralized bone matrix (DBM) have demonstrated
that healing occurs initially and principally by the direct induction and proliferation of osteoblasts derived principally
from resident mesenchymal stem cells of the dura, and to a lesser extent by resident mesenchymal stem cells of the connective
tissues beneath the skin flap. A small amount of cartilage is also synthesized after the direct process of ossification occurs.
To further confirm the molecular phenotypes of the repair cells in rat cranial defects, the present study evaluated mRNA expression
and synthesis of collagens I, II, and X and osteocalcin in the DBM-induced repair tissue by Northern blot analyses, autoradiography
after in vivo
3H-proline labeling of collagen, and immunohistochemistry. The results demonstrated that osteocalcin mRNA appeared in small
amounts by day 4 and continued to increase over the experimental period. Much lesser quantities of collagen types II and X
mRNAs appeared by day 6 and day 8, respectively. Collagen type I mRNA was present at all times examined but its expression
significantly increased by day 5. Autoradiographic and immunohistochemical studies showed that type II collagen was not detected
whereas type I collagen was synthesized on days 3–5. The data provide definitive molecular evidence confirming that the initial
and by far the major pathway of cranial defects repair induced by implantation of DBM is by the direct induction of resident
mesenchymal stem cells to osteoblasts and the direct formation of bone, which is spatially and temporarily distinct from the
later formation of cartilage.
Received: 30 November 1999 / Accepted: 21 March 2000 相似文献
896.
Mano M Arakawa T Mano H Nakagawa M Kaneda T Kaneko H Yamada T Miyata K Kiyomura H Kumegawa M Hakeda Y 《Calcified tissue international》2000,67(1):85-92
Prostaglandins (PGs) are well known to be important local factors in regulating bone formation and resorption. PGE2 is a potent stimulator of bone resorption because of enhancing osteoclast formation by its indirect action through stromal
cells. However, the direct action of PGE2 on functionally mature osteoclasts is still controversial. In this study using highly purified rabbit mature osteoclasts,
we examined the direct effect of PGE2 on osteoclastic bone-resorbing activity and its mechanism. PGE2 inhibited resorption pit formation on a dentine slice by the purified osteoclasts in a dose- and time-dependent manner. The
inhibitory effect appeared as early as 4 hours after the PGE2 addition. Forskolin and 12-0-tetradecanoyl phorbol-13-acetate (TPA), respective activators of adenylate cyclase and protein
kinase C, also decreased the osteoclastic bone-resorbing activity. PGE2 increased the content of intracellular cAMP in a dose range effective for the inhibition of bone resorption, whereas the
prostanoid did not alter the intracellular level of inositol triphosphate. The inhibition of osteoclastic bone resorption
by PGE2 was amplified and diminished by a cAMP phosphodiesterase inhibitor (isobutyl methylxanthine) and a protein kinase A inhibitor
(Rp-cAMP), respectively. Of four different subtypes of PGE2 receptors (EPs), EP4 mRNA was predominantly expressed in isolated osteoclasts, whereas the other types of EP mRNA were detected
in only small amounts. These results suggest that the PGE2 inhibitory effect was mediated by an adenylate cyclase system coupled with EP4. This possible association of PGE2 with EP4 in mature osteoclasts was supported by the finding that a specific agonist of EP4 (AE-604) inhibited the bone-resorbing
activity and elevated the intracellular cAMP content. However, butaprost, a selective EP2 agonist, also mimicked the PGE2 effects on isolated osteoclasts although EP2 mRNA expression was minimal. In conclusion, PGE2 directly inhibits bone-resorbing activity of functionally mature osteoclasts by activation of the adenylate cyclase system,
perhaps mainly through EP4.
Received: 21 July 1999 / Accepted: 31 January 2000 相似文献
897.
Gaumet-Meunier N Coxam V Robins S Pastoureau P Pointillart A Davicco MJ Lebecque P Barlet JP 《Calcified tissue international》2000,66(6):470-475
At 45 days of age, 40 male Wistar rats were castrated, then randomly divided into four groups, S.C. injected for 60 days
after surgery either with 17β-estradiol (E) 10 μg/kg BW/48 hours, progesterone (P) 140 μg/kg BW/48 hours, dihydrotestosterone
(D) 2 μg/kg BW/48 hours, E + P + D same doses, or solvent alone (CX). Ten other rats were sham-operated (SH) and used as controls.
Animals were put in balance to determine Ca and phosphorus (Pi) intestinal apparent absorption (IA Ca, IA Pi) and urinary
pyridinium crosslinks excretion. Plasma was collected for measurement of intact-parathyroid hormone (PTH), calcitonin (CT),
insulin-like growth factor I (IGF-I), 1,25 dihydroxyvitamin D (1,25(OH)2D), Ca, and Pi. Orchidectomy induced marked seminal vesicles atrophy and increased plasma CT, PTH, and Ca concentrations.
IA Ca was significantly higher in P rats, however, neither castration nor any other treatment had significant effects. Orchidectomy
decreased femoral length, dry weight, and Ca content, whereas E or D given alone or together with P improved endochondral
growth and enhanced femoral Ca content. Again, bone mineral density was lowered by orchidectomy and reestablished by both
E and EPD, even above SH values, this effect being more important at the metaphyseal levels. Urinary pyridinium cross-links
excretion and plasma osteocalcin concentrations were higher in the CX animals than in the controls. Although E and D given
alone did reduce both biochemical turnover markers, they showed additive effect when given together (EPD). In conclusion,
in the young castrated male rat, E was more efficient than D for preventing bone loss, the most important effect being induced
by a combination of E + P + D.
Received: 28 June 1999 / Accepted: 12 January 2000 相似文献
898.
Iwaniec UT Fung YK Cullen DM Akhter MP Haven MC Schmid M 《Calcified tissue international》2000,67(1):68-74
Limited research in young adults and immature animals suggests a detrimental effect of tobacco on bone during growth. This
study investigated the effects of nicotine, the major alkaloid component of tobacco, on calciotropic hormone concentrations
and bone status in growing female rats. One-month-old animals received either saline (n = 10), nicotine at 3.0 mg/kg/day (n
= 10), or nicotine at 4.5 mg/kg/day (n = 10) administered subcutaneously via osmotic minipumps for either 2 or 3 months. Sera,
femora, tibiae, and lumbar vertebrae (3–5) were collected at necropsy. The concentrations of serum calcium, phosphorus, 25-hydroxyvitamin
D, 1,25-dihydroxyvitamin D, parathyroid hormone, calcitonin, and insulin-like growth factor-I were determined. Bone variables
evaluated included mineral content and density (vertebrae and femora), cancellous and cortical histomorphometry (tibiae),
and bone strength (vertebrae and femora). Statistically significant differences in serum mineral and hormone concentrations
were not associated with nicotine dose or exposure time. No significant nicotine treatment effects were detected for bone
mineral content and density, bone histomorphometry, or bone strength. We conclude that nicotine treatment for 2 or 3 months
at serum concentrations in the upper range of those found in smokers has no detrimental effect on bone mass, volume, or strength
in the growing rat.
Received: 20 May 1999 / Accepted: 21 January 2000 相似文献
899.
The steroid sex hormones exert major effects on bone formation although the molecular events associated with their activity
remain unclear. We have investigated the effects of ovariectomy and dihydrotestosterone (DHT) administration to both sham-operated
and ovariectomized (ovx) rats on the bone mRNA levels of osteoblast genes. Rats were randomly allocated to either sham or
ovariectomy operations and were administered either vehicle or 40 mg/kg body weight DHT by silastic tube implants at the time
of operation for 8 weeks, at which time they were killed and total RNA was extracted from the long bones. Northern blot analysis
indicated that the mRNA levels of the bone cell genes α1(I) collagen, alkaline phosphatase, osteocalcin, and osteopontin were
markedly increased in ovx rats between 6- and 30-fold. DHT administration to ovary-intact, estrogen-sufficient rats increased
the mRNA levels of α1(I) collagen, alkaline phosphatase, osteopontin, and osteocalcin between 3- and 9-fold. In contrast,
DHT did not alter levels of these mRNA species in ovx rats. The data demonstrate that estrogen deficiency increased mRNA levels
of genes expressed during osteoblast development and suggest an interplay between estrogen and androgen action in regulating
the expression of a number of bone cell genes.
Received: 20 May 1999 / Accepted: 21 January 2000 相似文献
900.
Holmberg-Marttila D Sievänen H Järvinen TL Järvinen TA 《Calcified tissue international》2000,66(3):184-189
BsmI restriction fragment length polymorphism (RFLP) of the vitamin D receptor (VDR) gene and PvuII RFLPs of the estrogen receptor (ER) gene and their relation to changes in areal bone mineral density (BMD) were examined
in 43 healthy postpartum Finnish women aged 31.3 (SD 4.7) years. BMD was measured by dual energy X-ray absorptiometry at lumbar
spine, right femoral neck, and dominant distal radius immediately after delivery, 1 month after resumption of menses, and
1 year thereafter. The RFLPs were represented as Bb (BsmI) and Pp (PvuII), the capital letters denoting the absence of and the small letters the presence of the restriction sites. The frequency
of VDR alleles was as follows: bb (20.9%), Bb (60.5%), and BB (18.6%), and that of ER alleles was pp (39.5%), Pp (51.2%),
and PP (9.3%). Altogether, BMD decreased significantly during postpartum amenorrhea at all sites [the mean bone loss ranging
from −1.2 (SD 3.6)% at the distal radius to −3.7 (2.9)% at the femoral neck], and increased after resumption of menses [the
1-year follow-up BMD values ranging from −1.0 (2.4)% at the femoral neck to +3.3 (4.0)% at the lumbar spine as compared with
baseline]. No obvious genotype-related differences were found between these changes. These results suggest that the BsmI and PvuII polymorphisms may not have substantial influence on BMD changes postpartum.
Received: 20 November 1998 / Accepted: 30 September 1999 相似文献