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At least 865 records · Page 48Linked to original sources

PubMed1992

Isolation and characterization of human embryonic osteoblasts.

Human osteoblasts were obtained by migration and proliferation of cells from embryonic membranous bone on glass fragments. Light and electron microscopy analyses revealed a typical osteoblast-like appearance with high protein synthesis activity. The cells showed high alkaline phosphatase activity that was associated with plasma membranes and matrix vesicles and was 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] responsive. In contrast to the adult osteoblasts, embryonic cells could not produce detectable levels of osteocalcin, not even in the presence of 1,25(OH)2D3. Osteoblasts grown in multilayers produced a thick extracellular matrix, mainly composed of type I collagen, that mineralized in the presence of 10 mM beta-glycerophosphate. Because of their intrinsic osteogenic capacity, embryonic osteoblasts represent a valuable model for studying the mineralization process in vitro. In addition, the embryonic origin of these cells renders them a precious experimental system for the elucidation of mechanisms at the basis of differentiation of osteoblastic lineage.

Alkaline Phosphatase↗

PubMed1993

Comparative effect of cadmium on osteoblastic cells and osteoclastic cells.

Cadmium(Cd) has been thought to disturb the bone metabolism directly. The mechanism for the bone lesion is unknown, however. To examine the effects of cadmium on bone metabolism, we compared its effects on osteoblasts and osteoclasts in vitro. We used an established cell line, MC3T3-E1, as osteoblasts and tartrate resistant acid phosphatase (TRACP)-positive multi-nucleated cells (MNC) formed by a bone marrow culture system as osteoclasts. Alkaline phosphatase (ALP) activity was decreased by 10(-7) M Cd and DNA content and hydroxyproline content of osteoblastic cells were decreased by 10(-5) M Cd. Cadmium at 10(-7) M inhibited the osteoclastic cell formation from mouse bone marrow in the presence of 10(-8) M 1 alpha, 25(OH)2 vitamin D3. A 100-fold higher concentration of zinc(Zn) simultaneously added to the cadmium-containing medium prevented the toxicity of cadmium to osteoclastic cells as observed in the culture of osteoblastic cells. These results indicate that both bone formation and bone resorption are inhibited by cadmium. The responses of osteoclasts and osteoblasts to cadmium in this culture system were the same and the responses of cadmium-damaged osteoblasts and osteoclasts to zinc were also similar. These results suggest that another mechanism by which cadmium could cause bone damage should be considered in addition to the specific induction of osteoclastic cells by Cd.

Acid Phosphatase↗

PubMed1992

[The effect of static magnetic fields on osteoblast activity: an in-vitro study].

The aim of the present study was to investigate whether the influence of static magnetic fields can be demonstrated in an osteoblast cell culture. For this in-vitro study we used osteoblasts originating from the embryonal calvariae of rats. The total material (n = 41) was divided in four groups: a) cell cultures submitted to the fields of attracting magnets (n = 11), b) cell cultures in the fields of repelling magnets (n = 10), c) cell cultures under the influence of demagnetized magnets (sham group, n = 11), d) control cultures (n = 9). The cell cultures were subjected for 21 days to magnetic fields (intensity 178 ml) using Neodynium magnets. Osteoblast activity was histo-chemically determined by staining the alkaline phosphatase produced. The quantitative evaluation was performed by measuring the optical density of the cell cultures and the results were statistically analysed. The results of these in-vitro study are: 1. The optical density of the cell cultures was nearly the same in samples with or without the influence of magnetic fields. 2. No divergent reaction could be found between the application of homogeneous and heterogeneous magnetic fields. 3. The different orientation of homogeneous magnetic fields in vertical or horizontal direction did not effect the osteoblast cell culture. 4. The cellular distribution in the osteoblast cultures does not follow the orientation of the magnetic field lines. 5. The form of the osteoblasts was nearly the same among all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1975

Mitochondrial granules in human osteoblasts with a reference to one case of osteogenesis imperfecta.

Electron-dense granules in mitochondria from prenatal human osteoblasts, postnatal human osteoblasts, and from osteoblasts derived from a child with osteogenesis imperfecta congenita are described. The mitochondrial granules were of about 600 A in diameter and were attached to the mitochondrial cristae. Sections of mitochondria from prenatal osteoblasts showed an average number of 10 granuales per mitochondrial section, whereas sections of mitochondria of postnatal osteoblasts showed only occasionally 1-2 granules per mitochondrial section. Mitochondria from osteoblasts derived from the child with an untreated osteogenesis imperfecta congenita showed an average number of 10 granules per mitochondrial section.

Adolescent↗

PubMed1991

Does iron affect osteoblast function? Studies in vitro and in patients with chronic liver disease.

In order to study the role of trace elements as potential osteoblastic toxins, we measured bone aluminum, copper, and iron in 106 ambulant patients with histologically proven liver disease. We used analytical and histochemical methods and we correlated our results with serum biochemistry, forearm and spinal bone density, and dynamic bone histomorphometry. Patients with chronic liver disease had higher iron-stained perimeters than control subjects (P less than 0.001). However, the mean iron-stained perimeter was no greater than 5% of the total mineralized bone perimeter and did not correlate significantly with either the osteoblast perimeters or bone formation rates. The mean concentration of bone iron were 2.5 times (P less than 0.01) greater in the patients than in the controls although 80% of the patients fell within the normal range. There was a weak negative correlation between bone iron and the osteoblast perimeters (R = 0.18, P = ns) and between bone iron and bone formation (R = -0.30, P less than 0.05). There were 57 patients (56% of the total) with diminished bone formation, but only 16 had elevated bone iron concentrations. In a regression analysis, age, hypogonadism, and serum albumin concentrations were the most important predictors of osteoblast perimeters and bone formation rates. In vitro experiments using rat osteoblast-like osteosarcoma cells showed that an iron concentration of 400 mumol/liter was required to diminish cellular proliferation and function. Iron concentrations are elevated in the bones of patients with chronic liver disease. However, there is at present insufficient evidence that this metal is responsible for the osteoblast dysfunction seen in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1999

Prilocaine induces apoptosis in osteoblastic cells.

PURPOSE: To determine whether prilocaine, a local anesthetic, induces apoptosis in osteoblastic cells. METHODS: After reaching subconfluence, human osteoblastic Saos-2 and MG63 cells and mouse osteoblastic MC3T3-E1 cells were exposed for 48 hr to varying concentrations of prilocaine up to 10 mM and the cytotoxicity of the cells was analyzed by phase-contrast microscopy and WST-1 assay. Saos-2 cells treated for 48 hr with 5 mM prilocaine were stained with Hoechst 33342 and nuclear fragmentation was examined under a fluorescence microscope. DNA was extracted from the cells treated with 5 mM prilocaine and DNA ladder formation (a hallmark of apoptosis) was analyzed by agarose gel electrophoresis. RESULT: Prilocaine induced cell death in Saos-2 cells in a dose- and time-dependent manner up to the concentration of 10 mM. Marked nuclear condensation and fragmentation of chromatin were observed in the prilocaine-treated cells. DNA ladder formation also was induced by prilocaine treatment. Prilocaine-induced DNA ladder formation was dose-dependent with maximal effect at a concentration of 5 mM and was time-dependent from 12 to 48 hr. DNA ladder formation was also induced by prilocaine treatment in human osteoblastic MG63 cells and mouse osteoblastic MC3T3-E1 cells. Cycloheximide prevented prilocaine-induced apoptosis in Saos-2 cells in a dose-dependent fashion up to 20 microM as determined by WST-1 assay and DNA ladder formation in agarose gel electrophoresis. CONCLUSION: Osteoblastic cells treated with prilocaine exhibit both morphological and biochemical features indicative of apoptosis. The apoptotic mechanisms involve transcriptional regulation of specific proteins or protein synthesis.

Anesthetics, Local↗

PubMed2000

[In vivo administration of purified supernatant of fetal and postnatal osteoblast cultures: initial results].

With increasing age of an organism, the osseous regenerative potential is reduced. In osteoblast-like cell cultures, cells of older donors that would not proliferate under standard conditions start to proliferate and express a differentiated phenotype when supplemented with the supernatant of fetal osteoblast-like cultures. The aim of this study was an evaluation of the fetal supernatant actions in vivo. Rat calvaria-derived osteoblasts of fetal and 21-day-old donors were isolated enzymatically and cultured. Their osteoblastic phenotype was confirmed by the expression of typical osteoblast synthesis products. The supernatant of the cultures of each age group was collected and pooled. The supernatant was purified by HPLC and concentrated approximately ten times. Additionally, several age-dependent differences within the purified protein fractions were documented by MALDI. After resuspension, the purified supernatant proteins were transferred on a collagen carrier and implanted into critical size defects of the calvaria of adult Wistar rats. In a control group, the collagen carriers were implanted containing isotonic salt solution. After 2, 4, and 8 weeks, a radiographic and histologic analysis of the regeneration process was performed which revealed differences in the progress of mineralization. The methods used in this study might help to identify age-dependent differences regarding the osteoblastic synthesis of osteoanabolic peptides and their impact on the regeneration of osseous defects.

Age Factors↗

PubMed2006

Ultrastructural and metabolic changes in osteoblasts exposed to uranyl nitrate.

Exposure to uranium is an occupational hazard to workers who continually handle uranium and an environmental risk to the population at large. Since the cellular and molecular pathways of uranium toxicity in osteoblast cells are still unknown, the aim of the present work was to evaluate the adverse effects of uranyl nitrate (UN) on osteoblasts both in vivo and in vitro. Herein we studied the osteoblastic ultrastructural changes induced by UN in vivo and analyzed cell proliferation, generation of reactive oxygen species (ROS), apoptosis, and alkaline phosphatase (APh) activity in osteoblasts exposed to various UN concentrations (0.1, 1, 10, and 100 microM) in vitro. Cell proliferation was quantified by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, ROS was determined using the nitro blue tetrazolium test, apoptosis was morphologically determined using Hoechst 3332 and APh activity was assayed spectrophotometrically. Electron microscopy revealed that the ultrastructure of active and inactive osteoblasts exposed to uranium presented cytoplasmic and nuclear alterations. In vitro, 1-100 microM UN failed to modify cell proliferation ratio and to induce apoptosis. ROS generation increased in a dose-dependent manner in all tested doses. APh activity was found to decrease in 1-100 microM UN-treated cells vs. controls. Our results show that UN modifies osteoblast cell metabolism by increasing ROS generation and reducing APh activity, suggesting that ROS may play a more complex role in cell physiology than simply causing oxidative damage.

Alkaline Phosphatase↗

PubMed2003

Functional cooperativity between osteoblast transcription factors: evidence for the importance of subnuclear macromolecular complexes?

The accompanying article by Drs. Lian and Stein describes current thinking on how genes are organized in the nucleus and suggests that subnuclear localization is critical for the control of gene expression in bone. In particular, it is proposed that a major function of the osteoblast transcription factor, Runx2, is to tether genes that are active in osteoblasts to the nuclear matrix and serve as an organizing center for other nuclear factors which together form osteoblast-specific transcriptional units. Although it is still not established that the nuclear matrix localization function of Runx2 is essential for all its biological activities, there is no question that this factor plays a central role in mediating the response of osteoblasts to a variety of signals, as would be expected if Runx2 were involved in organizing the transcriptional apparatus. As will be discussed, Runx2 is required for the response of osteoblasts to other lineage-specific transcription factors and signals initiated by extracellular matrix-integrin binding, growth factors, hormones, and morphogens. We hypothesize that Runx2 transduces this wide range of responses by cycling between active, phosphorylated and a less active, dephosphorylated states which can selectively interact with other nuclear factors to form macromolecular complexes active in transcription. The possible relationship between these complexes and the subnuclear localization of the osteoblast transcriptional apparatus will also be discussed.

Animals↗

PubMed2004

Osteoblast-like cells complete osteoclastic bone resorption and form new mineralized bone matrix in vitro.

Bone remodeling involves old bone resorption by osteoclasts and new bone formation by osteoblasts. However, the precise cellular mechanisms underlying these consecutive events remain obscure. To address this question in vitro, we have established a cell culture model in which the resorption lacunae are first created by osteoclasts and osteoblast-like cells accomplish the subsequent bone formation. We isolated osteoclasts from rat bone marrow and cultured them on bovine bone slices for 48 hours to create resorption lacunae. After removing osteoclasts, confluent differentiated primary osteoblast cultures were trypsinized and the cells were replaced on the resorbed bone slices for up to 14 days. The cultures were then examined by confocal microscopy, field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM). Our data suggest that after osteoclastic bone resorption, osteoblast-like cells, not macrophages, remove the remaining organic matrix in the lacuna. After cleaning the lacuna, osteoblast-like cells deposit new collagen fibrils at the bottom of the lacuna and calcify the newly formed matrix only, as visualized by labeled tetracycline accumulation merely in the lacuna during the osteoblast culture. Furthermore, an electron-dense layer rich in osteopontin separates the old and new matrices suggesting formation of the cement line. Since the morphology of the newly formed matrix is similar to the natural bone with respect to the cement line and osteoid formation as well as matrix mineralization, the present method provides for the first time a powerful in vitro method to study the cellular mechanisms leading to bone remodeling also in vivo.

Animals↗

PubMed2004

Fluid shear stress induces beta-catenin signaling in osteoblasts.

beta-Catenin plays a dual role in cells: one at cell-cell junctions and one regulating gene transcription together with TCF (T-cell Factor) in the nucleus. Recently, a role for beta-catenin in osteoblast differentiation and gene expression has begun to be elucidated. Herein we investigated the effects of fluid shear stress (FSS) on beta-catenin signaling. FSS is a well-characterized anabolic stimulus for osteoblasts; however, the molecular mechanisms for the effects of this stimulation remain largely unknown. We found that 1 hour of laminar FSS (10 dynes/cm(2)) induced translocation of beta-catenin to the nucleus and activated a TCF-reporter gene. Analysis of upstream signals that may regulate beta-catenin signaling activity revealed two potential mechanisms for increased beta-catenin signaling. First, FSS induced a transient, but significant, increase in the phosphorylation of both glycogen synthase kinase 3beta (GSK-3beta) and Akt. Second, FSS reduced the levels of beta-catenin associated with N-cadherin, suggesting that less sequestration of beta-catenin by cadherins occurs in osteoblasts subjected to FSS. Functional analysts of potential genes regulated by beta-catenin signaling in osteoblasts revealed two novel observations. First, endogenous, nuclear beta-catenin purified from osteoblasts formed a complex with a TCF -binding element in the cyclooxygenase-2 promoter, and, second, overexpression of either a constitutively active beta-catenin molecule or inhibition of GSK-3beta activity increased basal cyclooxygenase-2 levels. Together, these data demonstrate for the first time that FSS modulates the activity of both GSK-3beta and beta-catenin and that these signaling molecules regulate cyclooxygenase-2 expression in osteoblasts.

3T3 Cells↗

PubMed2000

Bioglass 45S5 stimulates osteoblast turnover and enhances bone formation In vitro: implications and applications for bone tissue engineering.

We investigated the concept of using bioactive substrates as templates for in vitro synthesis of bone tissue for transplantation by assessing the osteogenic potential of a melt-derived bioactive glass ceramic (Bioglass 45S5) in vitro. Bioactive glass ceramic and bioinert (plastic) substrates were seeded with human primary osteoblasts and evaluated after 2, 6, and 12 days. Flow cytometric analysis of the cell cycle suggested that the bioactive glass-ceramic substrate induced osteoblast proliferation, as indicated by increased cell populations in both S (DNA synthesis) and G2/M (mitosis) phases of the cell cycle. Biochemical analysis of the osteoblast differentiation markers alkaline phosphatase (ALP) and osteocalcin indicated that the bioactive glass-ceramic substrate augmented osteoblast commitment and selection of a mature osteoblastic phenotype. Scanning electron microscopic observations of discrete bone nodules over the surface of the bioactive material, from day 6 onward, further supported this notion. A combination of fluorescence, confocal, transmission electron microscopy, and X-ray microprobe (SEM-EDAX) examinations revealed that the nodules were made of cell aggregates which produced mineralized collagenous matrix. Control substrates did not exhibit mineralized nodule formation at any point studied up to 12 days. In conclusion, this study shows that Bioglass 45S5 has the ability to stimulate the growth and osteogenic differentiation of human primary osteoblasts. These findings have potential applications for tissue engineering where this bioactive glass substrate could be used as a template for the formation of bioengineered bone tissue.

Alkaline Phosphatase↗

PubMed2000

Na+/Ca2+ exchanger isoforms of rat odontoblasts and osteoblasts.

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.

Amino Acid Sequence↗

PubMed1998

Estrogen effects on insulin-like growth factor gene expression in a human osteoblastic cell line with high levels of estrogen receptor.

Insulin-like growth factors (IGF)-I and IGF-II are produced by osteoblasts and are important paracrine/autocrine regulators of osteoblast proliferation and differentiation. Estrogen has been reported to increase gene expression of IGF-I in rodent osteoblasts. However, because species differences have been demonstrated in expression of various aspects of the IGF system in bone cells, it is not known whether this action also occurs in human osteoblasts. Thus, we assessed the effects of estrogen treatment on IGF-I and IGF-II gene expression in vitro in a recently developed human fetal osteoblast cell line that has high levels of estrogen receptors. As assessed by a quantitative reverse transcriptase-polymerase chain reaction method, treatment of hFOB/ER9 cells with 17beta-estradiol (E2) increased steady state levels of IGF-I mRNA in a time- and dose- dependent fashion with a maximal increase of 319% +/- 33% (P < 0.01) of control occurring after treatment with 10(-7) M E2 for 48 hours. In contrast, E2 did not alter steady state levels of IGF-II mRNA. The pure (type 2) antiestrogens ICI 182,780 (10(-7) M) and ICI 164,384 (10(-6) M) blocked the E2- induced increase in IGF-I mRNA levels. Interestingly, 4-hydroxytamoxifen (10(-7) M), a documented pure antiestrogen in reproductive tissues, also increased IGF-I mRNA to levels similar to those observed in E2-treated cells. Since E2 was shown to mediate its effects on some target genes through a cAMP-dependent pathway, we studied the interaction between E2 and agents that are known to increase intracellular cAMP. Forskolin (10(-8) M) and dibutyryl cAMP (10(-3) M) increased IGF-I mRNA levels sixfold, and cotreatment with E2 did not affect these changes, consistent with a possible mediation of the estrogen effect on IGF-I gene expression by cAMP. We conclude that in human osteoblastic cells, the IGF-I gene is a target for estrogen action, suggesting that IGF-I may mediate part of the effects of estrogen in human bone.

Bucladesine↗

PubMed1999

Hormonal regulation of the osteoblastic phenotype expression in neonatal murine calvarial cells.

Osteoblastic cell cultures from fetal rat calvariae have provided a popular model for studying the effects of dexamethasone (DEX) and 1, 25 dihydroxyvitamin D3 [1,25(OH)2D3] on gene expression but data from murine calvarial cells are scarce. Species-specific responses of rat and mouse osteoblastic cells to these hormones have been reported previously. In the present study, we investigated the effects of DEX and 1,25(OH)2D3 on expression of the osteoblastic phenotype by mouse calvarial cells. These murine osteoblast-like (MOB) cells expressed alkaline phosphatase (ALP) activity and osteocalcin and formed calcified nodules. Unlike the rat calvarial cells, ALP activities and nodule formation in MOB were inhibited by DEX. 1,25(OH)2D3 enhanced and DEX lowered the amount of osteocalcin synthesized by MOB. 1,25(OH)2D3 did not affect the number of nodules, but increased their sizes. Treating the cells for 2 days with only DEX at the beginning of the culture enhanced the effect of 1, 25(OH)2D3 on ALP. We found that in murine calvarial cells, DEX inhibits and 1,25(OH)2D3 enhances ALP activity, osteocalcin synthesis, and calcified nodule formation. This is in contrast to previous reports of rat calvarial cells where DEX is a positive and 1,25(OH)2D3 can be a negative regulator of the osteoblastic phenotype. These results suggest that profound species-specific differences exist between mice and rats in the regulation of the osteoblastic phenotype.

Alkaline Phosphatase↗

PubMed2005

Regulation of synthesis of osteoprotegerin and soluble receptor activator of nuclear factor-kappaB ligand in normal human osteoblasts via the p38 mitogen-activated protein kinase pathway by the application of cyclic tensile strain.

Mechanical stress is thought to play an important role in bone remodeling. However, the correlation between mechanical stress and bone remodeling is poorly understood. In this context, using a model of cyclic tensile strain (CTS) toward human osteoblasts, synthesis of osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and the activation of mitogen-activated protein kinases (MAPKs) were examined. The application of 7%, 0.25-Hz CTS once a day for 4 h for 3 successive days simultaneously caused an increase of OPG synthesis and a decrease of sRANKL release and RANKL mRNA expression in osteoblasts. As for MAPKs activation in osteoblasts with the application of CTS, p38 MAPK was activated 10-20 min after the application of CTS, but extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK) were not activated by such application. Furthermore, when CTS was applied once a day for 4 h for 1, 2, or 3 successive days to osteoblasts, p38 MAPK activation was maintained during the 3-day period but ERK1/2 activation was downregulated from day to day, simultaneously. Then, when CTS was applied once a day for 4 h for 3 successive days to osteoblasts pretreated with the p38 MAPK inhibitor SB203580 for 1 h, OPG synthesis was dose-dependently suppressed and inhibition of sRANKL release and RANKL mRNA expression was abrogated. These results indicate that biological responses of OPG and sRANKL synthesis in osteoblasts to the application of CTS are regulated via the p38 MAPK pathway and suggest that CTS might modulate and regulate bone metabolism.

Blotting, Western↗

PubMed2006

Murine osteoblasts respond to LPS and IFN-gamma similarly to macrophages.

Osteoblasts are bone-forming mesenchymal cells, while macrophages are cells of hematopoietic origin responsible for innate immunity. Lipopolysaccharide (LPS) can induce tolerance in macrophages, whereas interferon (IFN)-gamma can activate macrophages to produce cytokines, exert bactericidal effects, and present antigens. In this study, we examined such macrophagic phenotypes regulated by LPS and IFN-gamma in murine osteoblasts. In both primary calvarial osteoblasts and osteoblastic MC3T3-E1 cells, LPS pretreatment resulted in reduced production of IL-6 in response to a subsequent LPS stimulation or to Salmonella infection, indicating the existence of LPS-induced tolerance in osteoblasts. Furthermore, IFN-gamma treatment of MC3T3-E1 cells resulted in both enhanced IL-6 production in response to LPS and upregulation of major histocompatibility complex class II (MHC II). Following infection, Salmonella-containing vacuoles (SCVs) were formed in MC3T3-E1 cells, and IFN-gamma pretreatment enhanced bactericidal effects on intracellular Salmonella. Taken together, these observations indicate that osteoblasts can exhibit a subset of phenotypes reminiscent of macrophages in the course of bacterial infection.

Animals↗

PubMed2000

Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A.

The pluripotent mesenchymal stem cells give rise to osteoblasts, adipocytes, chondrocytes, and myoblasts. The differentiation of these stem cells into each of the mature functional cells may be controlled by a distinctive master gene(s) and is associated with temporal and spatial expression of diverse genes. Identification of genes that are expressed during the differentiation of the mesenchymal cells to osteoblasts is, therefore, important to obtain insights into the molecular mechanisms of osteogenesis. The murine undifferentiated mesenchymal cell 3T3-F442A, when treated with the bone morphogenetic protein 2 (BMP-2), a well-characterized inducer of mesenchymal cell differentiation, exhibited both osteoblastic and adipocytic differentiation. Using the SAGE (serial analysis of gene expression) technique, which has been shown to enable quantitative analysis of large numbers of genes in a simple and quick manner, we obtained 1600 sequence tags representing 2107 individual nucleotide sequences from control and BMP-2-treated 3T3-F442A cells, respectively. By comparing the frequency of tag occurrence, we found profiles of up- or downregulated genes associated with osteoblast or adipocyte phenotype such as type I collagen, osteonectin and OSF-2, or C/EBPbeta, aP2, fatty acid synthase, and lipoprotein lipase, respectively, in BMP-2-treated 3T3-F442A cells. Our data show that BMP-2 induces not only osteoblastic but also adipocytic differentiation in the 3T3-F442A cells. They also show that the 3T3-F442A cells have bipotentials of differentiating toward osteoblasts and adipocytes. The results, therefore, might explain the inverse correlation between trabecular bone volume and fat volume in the bone marrow cavity. The results also suggest that the SAGE may be a useful technique that allows us a fast and efficient way to generate global and local views of gene expression associated with cellular differentiation of the mesenchymal stem cells.

3T3 Cells↗