共查询到20条相似文献,搜索用时 15 毫秒
1.
Endochondral bone formation occurs through a series of developmentally regulated cellular stages, from initial formation
of cartilage tissue to calcified cartilage, resorption, and replacement by bone tissue. Nasal cartilage cells isolated by
enzymatic digestion from rat fetuses were seeded at a final density of 105 cell/cm2 and cultured in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal calf serum in the presence of ascorbic
acid and β-glycerophosphate. First, cells lost their phenotype but in this condition they rapidly reexpressed the chondrocyte
phenotype and were able to form calcified cartilaginous nodules with the morphological appearance of cartilage mineralization
that occurs in vivo during endochondral ossification. In this mineralizing chondrocyte culture system, we investigated, between day 3 and day
15, the pattern expression of types II and X collagen, proteoglycan core protein, characteristic markers of chondrocyte differentiation,
as well as alkaline phosphatase and osteocalcin associated with the mineralization process. Analysis of labeled collagen and
immunoblotting revealed type I collagen synthesis associated with the loss of chondrocyte phenotype at the beginning of the
culture. However, our culture conditions promoted extracellular matrix mineralization and cell differentiation towards the
hypertrophic phenotype. This differentiation process was characterized by the induction of type X collagen mRNA, alkaline
phosphatase, and diminished expression of type II collagen and core protein of large proteoglycan after an increase in their
mRNA levels before the mineralizing process. These results revealed distinct switches of the specific molecular markers and
indicated a similar temporal expression to that observed in vivo recapitulating all stages of the differentiation program in vitro.
Received: 12 December 1996 / Accepted: 26 June 1997 相似文献
2.
Acceleration of Fresh Fracture Repair Using the Sonic Accelerated Fracture Healing System (SAFHS): A Review 总被引:5,自引:0,他引:5
The Sonic Accelerated Fracture Healing System (SAFHS) is a relatively new fracture management tool which incorporates the
application of a specifically modified diagnostic ultrasound unit to healing fractures with the intention of accelerating
repair. In an animal fracture model, this device has been shown to accelerate the rate of biomechanical healing by a factor
of 1.4–1.6. In two randomized, controlled trials in humans, the same unit has been shown to reduce the time frame of clinical
and radiographic healing by 38%. In the two fracture regions investigated, tibial diaphysis and distal radius, this represented
a 58 day and 37 day reduction in healing time, respectively. Despite its effect on the entire process of fresh fracture repair,
the effect of the SAFHS on the individual stages and processes involved has not been established. This paper reviews these
stages and processes, and discusses the clinical and practical implications of the effect of the SAFHS on fracture repair
and the need for further research into this modality.
Received: 24 December 1998 / Accepted: 13 August 1999 相似文献
3.
Jämsä T Koivukangas A Kippo K Hannuniemi R Jalovaara P Tuukkanen J 《Calcified tissue international》2000,66(4):288-291
Fracture healing and callus formation have traditionally been evaluated by using X-ray radiography. Here we compared X-ray
radiography and peripheral quantitative computed tomography (pQCT) in evaluating the healing callus of standardized tibial
fractures in 141 female rats after a 4- or 8-week follow-up. The results were compared with the tensile (4-week) and compressive
(8-week) failure load of the callus. The projectional size of callus, as defined from lateral ex vivo radiographs, correlated
significantly with the pQCT-defined cross-sectional area (CSA) of mid-callus. This relationship was dependent on the pQCT
attenuation threshold, being higher for the CSA of compact bone (r = 0.85, P < 0.0001) than for the total bone CSA (r = 0.68, P < 0.0001). Radiographically defined callus projectional area also correlated strongly with bone mineral content (BMC) (r
= 0.84–0.86, P < 0.0001). The mean optical density of the callus analyzed from the radiographs had only a weak correlation with the pQCT-defined
bone mineral density (BMD) of callus. A weak negative relationship was found between CSA and BMD. The optical density analyzed
from lateral radiographs did not correlate with the tensile or compressive failure load of callus. Callus size, BMC, and BMD
were associated with the compressive failure load, whereas both radiographs and pQCT were poor in explaining the failure load
in tension.
Received: 28 June 1999 / Accepted: 28 October 1999 相似文献
4.
During endochondral ossification, proliferative activity of chondrocytes is arrested and the cells undergo terminal hypertrophic
differentiation. We examined the expression of the cyclin-dependent kinase inhibitor, p21CIP1/WAF1 in permanent cartilage (xyphoid and articular cartilage) and in cartilage undergoing endochondral ossification (growth plate,
epiphyseal ossification centers, and costochondral junctions) to determine if p21 is up-regulated in chondrocytes during hypertrophic
differentiation. Northern blot analyses demonstrated expression of p21 in chondrocytes undergoing endochondral ossification
and from sites of permanent cartilage. Quantitative analyses of Northern data showed an association between expression of
the hypertrophic-specific marker, collagen type X, and the level of 21 expression. In situ hybridization of rodent femoropatellar joints and costochondral junctions localized p21 mRNA to chondrocytes within both
the proliferative and hypertrophic zones of the growth plates, in chondrocytes involved in formation of the epiphyseal ossification
centers, and in articular chondrocytes. Immunohistochemical analyses of p21 expression in the same tissues demonstrated comparatively
higher levels of p21 protein in postmitotic chondrocytes. These data suggest that p21 is active in cell cycle regulation in
chondrocytes, and that increased p21 expression is associated with hypertrophic differentiation.
Received: 11 October 1996 / Accepted: 23 April 1997 相似文献
5.
目的 探究Indian Hedgehog(IHH)信号通路对软骨内成骨过程中软骨细胞成熟以及转分化的影响。方法 取10日龄野生型小鼠的胫骨组织,采用原位杂交和免疫组织化学染色检测生长板区域IHH信号通路相关分子Ihh、Ptch1和Gli1的表达水平。构建肥大软骨细胞特异性Ihh基因敲除小鼠(Col10a1Cre/+; Ihhnull/C),并采用影像学检查和阿利新蓝染色评估该小鼠的骨骼发育状况。构建肥大软骨细胞IHH信号通路持续激活小鼠(Col10a1Cre/+; R26SmoM2/M2和 Col10a1Cre/+; Ptch1LacZ/C),采用HE染色、原位杂交和TUNEL染色分别对受精15.5天胎鼠胫骨组织形态结构、Ihh(肥大软骨细胞分子标志物)和Col1a1(成骨细胞分子标志物)以及肥大软骨细胞凋亡水平进行检测;另外应用HE染色对10日龄小鼠的胫骨组织进行组织学分析。结果 肥大软骨细胞合成分泌IHH,但不表达Ptch1和Gli1。抑制肥大软骨细胞合成IHH蛋白会导致出生后小鼠出现侏儒症;X线检查结果显示小鼠出现严重的骨骼发育不良,包括胸廓狭小、球形头骨以及椎骨发育异常等表现。持续启动IHH信号通路时,胚胎早期软骨细胞成熟分化过程虽未见异常,但是出生后小鼠的骨小梁、骨内膜以及皮质骨等结构均出现一定的异常表现。结论 IHH信号通路虽然不参与肥大软骨细胞的终末分化过程,但在软骨细胞转分化的过程中起到了重要的调控作用。 相似文献
6.
Uusitalo H Hiltunen A Söderström M Aro HT Vuorio E 《Calcified tissue international》2000,67(5):382-390
Fracture repair provides an interesting model for chondrogenesis and osteogenesis as it recapitulates in an adult organism
the same steps encountered during embryonic skeletal development and growth. The fracture callus is not only a site of rapid
production of cartilage and bone, but also a site of extensive degradation of their extracellular matrices. The present study
was initiated to increase our understanding of the roles of different proteolytic enzymes, cysteine cathepsins B, H, K, L,
and S, and matrix metalloproteinases (MMPs) 9 and 13, during fracture repair, as this aspect of bone repair has previously
received little attention. Northern analysis revealed marked upregulation of cathepsin K, MMP-9, and MMP-13 mRNAs during the
first and second weeks of healing. The expression profiles of these mRNAs were similar with that of osteoclastic marker enzyme
tartrate-resistant alkaline phosphatate (TRAP). The changes in the mRNA levels of cathepsins B, H, L, and S were smaller when
compared with those of the other enzymes studied. Immunohistochemistry and in situ hybridization confirmed the predominant localization of cathepsin K and MMP-9 and their mRNA in osteoclasts and chondroclasts
at the osteochondral junction. MMP-13 was present in osteoblasts and individual hypertrophic chondrocytes near the cartilage-bone
interphase. In cartilaginous callus, the expression of cathepsins B, H, L, and S was mainly related to chondrocyte hypertrophy.
During bone remodeling both osteoblasts and osteoclasts contained these cathepsins. The present data demonstrate that degradation
and remodeling of extracellular matrices during fracture healing involves activation of MMP-13 production in hypertrophic
chondrocytes and osteoblasts, and cathepsin K and MMP-9 production in osteoclasts and chondroclasts.
Received: 2 February 2000 / Accepted: 25 May 2000 / Online publication: 2 November 2000 相似文献
7.
We have previously shown that restoration of a local bone defect in the rat not only leads to a regional acceleratory phenomenon
(RAP), but also to a systemic acceleration of osteogenesis (SAP) at distant sites of the skeleton. In this study, we investigated
whether specific inhibition of osteoblasts would affect the local RAP and the systemic acceleratory phenomenon (SAP) healing
sites. Systemic inhibition of osteoblasts was induced by inflammation-mediated osteopenia (IMO), a nonspecific type of inflammation
initiated by S.C. injections of sterile talc. A drill hole defect 1.2 mm in diameter was performed at the midshaft of the
left tibia of female rats. On day 7, during the formation phase of the local healing process, IMO did not influence the number
of osteoblasts or the bone volume in the marrow cavity of the local healing site, whereas it did lead to a significant reduction
of osteoblast number and bone volume at the systemic site (subepiphyseal spongiosa of the tibia). By contrast, on days 14
and 21, during the resorption phase of bone healing, IMO led to a significant reduction in both osteoblast number and bone
volume in the marrow cavity of the local healing site. At the same time, however, it did not influence the cortical area of
the bone defect where newly formed bone is needed to ensure mechanical stability. In summary, our model of bone healing reveals
that a humoral noxious osteoblast stimulus such as IMO is able to inhibit systemically osteoblasts stimulated by SAP, whereas
it is not able to inhibit osteoblasts either from producing woven bone during a RAP or from producing bone that is needed
to mechanically stabilize a defect.
Received: 31 March 1997 / Accepted: 20 February 1998 相似文献
8.
I. Berdud A. Martin-Malo Y. Almaden P. Aljama M. Rodriguez A. J. Felsenfeld 《Calcified tissue international》1998,62(5):457-461
To establish the PTH dosage that maintains normal mineral homeostasis in the PTX rat, a series of doses of rat 1-34 PTH were
infused via a subcutaneously implanted miniosmotic pump. The doses were 0, 0.011, 0.022, 0.044, and 0.11 μg/100 g/hour. After
48 hours, serum calcium ranged from 5.56 ± 0.02 to 16.29 ± 0.25 mg/dl, ANOVA P < 0.001, and serum phosphorus from 12.49 ± 0.03 to 5.33 ± 0.34 mg/dl, ANOVA P < 0.001. By post hoc test, the serum calcium level was different (P < 0.05) at every PTH dose; the serum phosphorus level was different (P < 0.05) at every PTH dose except between the two highest doses. The PTH dosage that produced a normal serum calcium (10.09
± 0.10 mg/dl) and phosphorus (6.90 ± 0.18 mg/dl) was 0.022 μg/100 g/hour. The relationship between increasing doses of PTH
and both serum calcium and phosphorus was curvilinear and the calcium-phosphorus product was remarkably constant from a serum
calcium of 7–13 mg/dl. The increase in serum calcium and the decrease in serum phosphorus were more rapid at lower than at
higher PTH doses so that for both, an asymptote was reached. At the highest serum calcium values, the calcium-phosphorus product
increased and in individual rats, an increase in serum phosphorus was associated with a decrease in serum calcium. In summary,
this study shows that (1) for rat 1-34 PTH, the normal replacement dose in the PTX rat with normal renal function on a normal
diet is 0.022 μg/100 g/hour; (2) the relationship between PTH and both serum calcium and phosphorus is curvilinear, and an
asymptote is reached for both; and (3) the calcium-phosphorus product is remarkably constant as the serum calcium increases
from 7 to 13 mg/dl and only increased during marked hypercalcemia when serum phosphorus did not decrease further or even tended
to increase.
Received: 30 May 1997 / Accepted: 15 October 1997 相似文献
9.
Hip fracture, the most dramatic complication of osteoporosis, constitutes a serious health problem of the elderly, with great
socioeconomic consequences. Hip fracture epidemiology has been studied by many investigators. Until now, reported studies
in Greece include either data from only one region, or they do not include all the epidemiological parameters concerning hip
fractures. We studied hip fractures that occurred in Greece in 1992 and compared the findings with those of previous years
(1977, 1982, 1987), in order to identify age and sex incidence and increase rate during 1977–1992. There has been an average
annual increase of 7.6%, thus total hip fractures in Greece increased from 5,100 in 1977 (54.75 fractures/100,000 inhabitants)
to 10,953 in 1992 (107.30 fractures/100,000 inhabitants). In 1992, 70% of the patients were women. During the 1977–1992 period,
age-adjusted incidence for people aged over 50 increased in both sexes (from 173.54 fractures/100,000 inhabitants in 1977
to 314.07 fractures/100,000 inhabitants in 1992, an increase of age-adjusted incidence of 80.97%). Approximately 50% of the
patients in 1992 were aged 80 and over, whereas in 1977 there were only 22.49% patients of the same age. The increase in hip
fracture numbers is greater than expected due to population aging, suggesting the existence of other factors influencing this
increase. The most affected age group is 80 and over.
Received: 3 June 1997 / Accepted: 9 October 1997 相似文献
10.
Chondrocyte Differentiation in Human Osteoarthritis: Expression of Osteocalcin in Normal and Osteoarthritic Cartilage and Bone 总被引:5,自引:0,他引:5
Pullig O Weseloh G Ronneberger D Käkönen S Swoboda B 《Calcified tissue international》2000,67(3):230-240
Osteocalcin (OC), which is a marker of the mature osteoblasts, can also be found in posthypertrophic chondrocytes of the
epiphyseal growth plate, but not in chondrocytes of the resting zone or in adult cartilage. In human osteoarthritis (OA),
chondrocytes can differentiate to a hypertrophic phenotype characterized by type X collagen. The protein- and mRNA-expression
pattern of OC was systematically analyzed in decalcified cartilage and bone sections and nondecalcified cartilage sections
of human osteoarthritic knee joints with different stages of OA to investigate the differentiation of chondrocytes in OA.
In severe OA, we found an enhanced expression of the OC mRNA in the subchondral bone plate, demonstrating an increased osteoblast
activity. Interestingly, the OC protein and OC mRNA were also detected in osteoarthritic chondrocytes, whereas in chondrocytes
of normal adult cartilage, both the protein staining and the specific mRNA signal were negative. The OC mRNA signal increased
with the severity of OA and chondrocytes from the deep cartilage layer, and proliferating chondrocytes from clusters showed
the strongest signal for OC mRNA. In this late stage of OA, chondrocytes also stained for alkaline phosphatase and type X
collagen. Our results clearly show that the expression of OC in chondrocytes correlates with chondrocyte hypertrophy in OA.
Although the factors including this phenotypic shift in OA are still unknown, it can be assumed that the altered microenvironment
around osteoarthritic chondrocytes and systemic mediators could be potential inducers of this differentiation.
Received: 20 May 1999 / Accepted: 10 February 2000 相似文献
11.
B. Herbert A. Lecouturier D. Masquelier N. Hauser C. Remacle 《Calcified tissue international》1997,60(2):216-223
Two methods of collecting osteoblast-like cells from newborn rat calvaria were tested, either placing individual glass fragments
or tipping dense glass beads onto the endocranial surface of periosteum-free bone. Inoculated at high density, cells collected
by using these two methods form large mineralized plates after three weeks of culture. The main purpose of our investigation
was to analyze the progressive formation of this mineralized structure and to localize alkaline phosphatase activity. At the
beginning of the culture, flattened cells gathered into multilayers and synthesized collagen fibers. Cells in the upper layer
became rapidly cuboidal in shape and continued to secrete collagen at their basal pole, whereas other cells became progressively
embedded in the extracellular matrix. The upper cells featured ultrastructural characters of osteoblasts, whereas the embedded
cells resembled osteocytes. After two weeks, the matrix began to mineralize: crystals appeared on collagen fibers, on matrix
vesicles, and on cell debris. During the first days of the culture, the alkaline phosphatase activity was localized on the
plasma membranes and on the collagen fibers. Thereafter, only the upper cells and collagen fibers that were juxtaposed to
these cells showed alkaline phosphatase activity. In addition, the presence of mineralized matrix prevented the reaction product
from being visualized on collagen fibers. The ultrastructural analysis reveals large mineralized plates with a structure resembling
that of bone in vivo. This culture appears to be an appropriate model to study bone formation and regulation.
Received: 30 September 1995 / Accepted: 3 May 1996 相似文献
12.
In odontoblasts as well as osteoblasts, a number of mechanisms for the inflow and extrusion of Ca2+ have been demonstrated. The entrance of Ca2+ ions into odontoblasts occurs mainly through voltage-gated calcium channels. Extrusion of Ca2+ is found to be an ATP-dependent process and, in addition, Na+/Ca2+-antiports exist, which are provoked by extracellular Na+. The aim of this study was to identify the Na+/Ca2+-antiport isoforms expressed in dentinogenically active rat incisor odontoblasts and to make a comparison with different osteoblastic
cells. Using RT-PCR and RNAse protection assay, we demonstrated the expression of three different isoforms, NaCa 3, 7, and
10, of the NCX1-encoded antiport in odontoblasts and osteoblastic cells. When incubated in the presence of Na+, dissected rat incisor odontoblasts as well as the osteoblastic cells extruded Ca2+ ions, as detected by chlorotetracycline and Fura-2 fluorometry, thus supporting a physiological role for the detected isoform
expression. Odontoblasts and rat calvarial osteoblasts, as well as osteoblast-like cell lines UMR-106.01 and Saos-2, were
shown to exhibit identical phenotypes of Na+/Ca2+-antiport isoform expression, different from the expression patterns of other tissues. The significance of this specific expression
pattern is unknown, but there is a possibility that it is in some way related to the unique demands on these cell types to
produce mineralized connective tissue.
Received: 8 May 1999 / Accepted: 21 January 2000 相似文献
13.
14.
C. Kasperk A. Helmboldt I. Börcsök S. Heuthe O. Cloos F. Niethard R. Ziegler 《Calcified tissue international》1997,61(6):464-473
There are obvious sexual differences in adult skeletal morphology which for the most part are related to differences in size.
Higher androgen serum levels in males exert potent osteoanabolic effects and therefore may contribute to this sexual dimorphism
of the skeleton. The presence of androgen receptors (AR) in bone cells is a prerequisite for a direct osteoanabolic action
of androgens. To investigate the possibility that, in addition to gender-related differences in androgen serum levels, there
are also gender-related differences in the osteoblastic expression pattern of the androgen receptor, we examined AR mRNA expression,
androgen binding sites, and mitogenic responses to the androgen dihydrotestosterone (DHT) in human osteoblastic cell (HOC)
populations. HOCs were isolated from bone biopsy specimens derived from different skeletal sites of healthy adult males and
females (2–69 years old). We found that male and female HOCs of all examined ages express similar AR mRNA levels and similar
numbers of androgen binding sites. Using whole-cell-binding assays, we observed 3129–8417 androgen binding sites per femoral
HOC with apparent KDs of 1.45–2.83 nM depending on the age of the investigated HOC population. Mandibular and cortical HOC
of both sexes expressed higher AR mRNA levels, significantly more androgen binding sites per cell, and exhibited significantly
greater mitogenic responses to DHT than iliac crest-derived and trabecular HOC of the same skeletal system and the same skeletal-site,
respectively. In early adulthood, HOCs of both sexes appear to express somewhat higher AR mRNA levels and to possess more
androgen binding sites than prepubertal and senescent HOC. Because sex hormone serum levels rise in puberty, we investigated
the regulation of the AR mRNA expression by various steroids. We found that dexamethasone (dexa) and in some experiments also
17β-estradiol (E2) and 1,25-dihydroxyvitamin D3 (D3) increased AR mRNA levels and androgen binding in HOC cultures. A pretreatment
with dexa, E2, and D3 significantly increased the mitogenic response of HOCs to DHT. We conclude that (1) higher androgen
serum levels in males together with a higher AR expression at certain skeletal sites may contribute to the development of
sex-related differences in skeletal morphology, (2) glucocorticoids induce AR gene expression in HOC cultures, and (3) glucocorticoids,
E2, and D3 enhance the mitogenic action of DHT.
Received: 3 June 1996 / Accepted: 30 April 1997 相似文献
15.
The small proteoglycan decorin had been localized previously at the d-band in the gap zone of collagen fibrils in nonmineralizing
tissues. In bone matrix this zone is proteoglycan free and is at least in some species the place where mineralization along
collagen fibrils starts. To study the metabolism of the small proteoglycans decorin and biglycan under mineralizing conditions,
osteoblasts from human nasal bone were cultured for several weeks in the presence or absence of β-glycerophosphate and ascorbate.
An immediate consequence of the treatment was a reduced expression of decorin, as judged by immune precipitation, whereas
the biosynthesis of biglycan was not affected. Pulse-chase experiments were performed with osteoblasts embedded in floating
type I collagen gels. In the presence of β-glycerophosphate and ascorbate, a more rapid turnover of both proteoglycans was
noted; the one of biglycan reached statistical significance. Indirect evidence for an enhanced rate of proteoglycan endocytosis
was obtained. This effect was not seen in cultured skin fibroblasts. Thus, osteoblasts respond rapidly to mineralizing conditions
with alterations of small proteoglycan biosynthesis and turnover.
Received: 30 October 1995 / Accepted: 3 January 1997 相似文献
16.
T Onishi Y Ishidou T Nagamine K Yone T Imamura M Kato T.K Sampath P ten Dijke T Sakou 《BONE》1998,22(6):605-612
Bone morphogenetic proteins (BMPs) and their receptors (BMPRs) are thought to play an important role in bone morphogenesis. The purpose of this study was to determine the locations of BMP-2/-4, osteogenic protein-1 (OP-1, also termed BMP-7), and BMP type II receptor (BMPR-II) during rat fracture healing by immunostaining, and thereby elucidate the possible roles of the BMPs and BMPR-II in intramembranous ossification and endochondral ossification. In the early stage of fracture repair, the expression of BMP-2/-4 and OP-1 was strongly induced in the thickened periosteum near the fracture ends, and coincided with an enhanced expression of BMPR-II. On day 7 after fracture, staining for BMP-2/-4 and OP-1 immunostaining was increased in various types of chondrocytes, and was strong in fibroblast-like spindle cells and proliferating chondrocytes in endochondral bone. On day 14 after fracture, staining with OP-1 antibody disappeared in proliferating and mature chondrocytes, while BMP-2/-4 staining continued in various types of chondrocytes until the late stage. In the newly formed trabecular bone, BMP-2/-4 and OP-1 were present at various levels. BMPR-II was actively expressed in both intramembranous ossification and endochondral ossification. Additionally, immunostaining for BMP-2/-4 and OP-1 was observed in multinucleated osteoclast-like cells on the newly formed trabecular bone, along with BMPR-II. In reference to our previous study of BMP type I receptors (BMPR-IA and BMPR-IB), BMPR-II was found to be co-localized with BMPR-IA and BMPR-IB. BMP-2/-4 and OP-1 antibodies exhibited distinct and overlapping immunostaining patterns during fracture repair. OP-1 may act predominantly in the initial phase of endochondral ossification, while BMP-2/-4 acts throughout this process. Thus, these findings suggested that BMPs acting through their BMP receptors may play major roles in modulating the sequential events leading to bone formation. 相似文献
17.
18.
M. Ito T. F. Lang M. Jergas M. Ohki M. Takada T. Nakamura K. Hayashi H. K. Genant 《Calcified tissue international》1997,61(2):123-128
This study examined trabecular bone mineral density (BMD) in Japanese women with and without spinal fracture, and compared
the results to American women with and without fracture. The quantitative computed tomography (QCT) systems used at the University
of California, San Francisco (UCSF) and at Nagasaki University were cross-calibrated. Normative BMD was assessed with the
K2HPO4 liquid phantom in 538 Americans aged 20–85 years, and with the B-MAS200 phantom in 577 Japanese aged 20–83 years. These BMD
were adjusted for use with the Image Analysis solid phantom using the result of cross-calibration. The trabecular BMD in 111
postmenopausal American women (55 with fracture), and in 185 postmenopausal Japanese women (67 with fracture) were compared
for investigation of the difference in BMD values relative to fracture status. The absolute BMD values in Japanese were lower
than those in Americans, and the differences were greater with advancing age. The magnitude of the BMD difference was 8.6,
20.5, 38.1 mg/cm3 in women aged 20–24 years, 40–44 years, 60–64 years, respectively. In premenopausal women, BMD began to decrease at the age
of 20 in Japanese, whereas the peak bone mass was maintained until the age of 35 in the American women. In immediate postmenopausal
women, BMD significantly decreased in both populations. In later postmenopausal women, BMD significantly decreased with age
in the Japanese women but decreased less rapidly in the American women. The aging decrease of BMD was 1.4% and 2.2% per year
in the later postmenopausal American and Japanese women, respectively. The fracture threshold is considered to be lower in
Japanese women. However, the BMD difference between American and Japanese women with fracture was similar to that without
fracture. The Z-scores of fracture subjects versus controls were 2.9 in American and 1.8 in Japanese women. In conclusion,
Japanese women were found to have a lower BMD and lower fracture threshold than American women. The significant decrease of
spinal trabecular BMD in late postmenopause is potentially responsible for the higher prevalence of spinal fracture in Japanese
women.
Received: 18 December 1995 / Accepted: 23 September 1996 相似文献
19.
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
20.
Expression of BMP-2 by Rat Bone Marrow Stromal Cells in Culture 总被引:7,自引:0,他引:7
To investigate the role of bone morphogenetic protein (BMP-2) in ossifying rat bone marrow stromal cell cultures, we determined
the population of fibroblast-like stromal cells that expressed BMP-2 immunocytochemically (anti-rhBMP-2 monoclonal antibody),
and compared that to alkaline phosphatase (AP) and collagen synthesis formed in culture over a 4-week period in control and
dexamethasone-supplemented mineralizing media. In control media, the percentage of BMP-2-positive stromal cells (BMP-2+) increased from 12 to 25% within the first 4 days of culture. In mineralizing media, the level of BMP-2+ cells was significantly increased (43–44%). The intensity of immunostaining gradually increased with time. The levels of
AP were undetectable at 1 week in both control and mineralizing media, but increased gradually over the next 2 weeks and peaked
at 3 weeks. ALP levels were significantly greater in cultures grown in mineralizing medium (P < 0.05 at 3 weeks, P < 0.01 at 4 weeks). Collagen synthesis peaked and was significantly greater at 3 weeks (P < 0.05) in cultures grown in mineralizing medium. The levels of AP and collagen synthesis most closely reflected the changes
in the percentage of BMP-2+ cells from 7 to 28 days. Though these changes may reflect a primary action of BMP-2 on marrow osteoprogenitor-like stromal
cells, they do not exclude a mechanism that involves the induction of other members of the BMP family known to stimulate AP
and collagen synthesis. We conclude that BMP-2 expression in cultures of fibroblast-like marrow stromal cells is enhanced
when those cells are induced to become osteoblasts by exposure to dexamethasone.
Received: 30 October 1997 / Accepted: 24 June 1998 相似文献