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Jenneke Kleinnulend - One of the best experts on this subject based on the ideXlab platform.
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Bone Cell mechanosensitivity estrogen deficiency and osteoporosis
Journal of Biomechanics, 2015Co-Authors: Jenneke Kleinnulend, Rene F M Van Oers, Astrid D Bakker, Rommel G. BacabacAbstract:Adaptation of Bone to mechanical stresses normally produces a Bone architecture that combines a proper resistance against failure with a minimal use of material. This adaptive process is governed by mechanosensitive osteocytes that transduce the mechanical signals into chemical responses, i.e. the osteocytes release signaling molecules, which orchestrate the recruitment and activity of Bone forming osteoblasts and/or Bone resorbing osteoclasts. Computer models have shown that the maintenance of a mechanically-efficient Bone architecture depends on the intensity and spatial distribution of the mechanical stimulus as well as on the osteocyte response. Osteoporosis is a condition characterized by a reduced Bone mass and a compromized resistance of Bone against mechanical loads, which has led us to hypothesize that mechanotransduction by osteocytes is altered in osteoporosis. One of the major causal factors for osteoporosis is the loss of estrogen, the major hormonal regulator of Bone metabolism. Loss of estrogen may increase osteocyte-mediated activation of Bone remodeling, resulting in impaired Bone mass and architecture. In this review we highlight current insights on how osteocytes perceive mechanical stimuli placed on whole Bones. Particular emphasis is placed on the role of estrogen in signaling pathway activation by mechanical stimuli, and on computer simulation in combination with Cell biology to unravel biological processes contributing to Bone strength.
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are affected by mechanical loading, which is thought to provoke a Cellular response via loading-induced flow of interstitial fluid. Adipose tissue is an easily accessible source of mesenchymal stem Cells for Bone tissue engineering, and is available in abundant amounts compared with Bone marrow. We studied whether adipose tissue-derived mesenchymal stem Cells (AT-MSCs) are responsive to mechanical loading by pulsating fluid flow (PFF) on osteogenic stimulation in vitro. We found that ATMSCs show a Bone Cell-like response to fluid shear stress as a result of PFF after the stimulation of osteogenic differentiation by 1,25-dihydroxyvitamin D3. PFF increased nitric oxide production, as well as upregulated cyclooxygenase-2, but not cyclooxygenase-1, gene expression in osteogenically stimulated AT-MSCs. These data suggest that AT-MSCs acquire Bone Cell-like responsiveness to pulsating fluid shear stress on 1,25-dihydroxyvitamin D3-induced osteogenic differentiation. ATMSCs might be able to perform Bone Cell-specific functions during Bone (re)modeling in vivo and, therefore, provide a promising new tool for Bone tissue engineering.
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are ...
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are affected by mechanical loading, which is thought to provoke a Cellular response via loading-induced flow of interstitial fluid. Adipose tissue is an easily accessible source of mesenchymal stem Cells for Bone tissue engineering, and is available in abundant amounts compared with Bone marrow. We studied whether adipose tissue-derived mesenchymal stem Cells (AT-MSCs) are responsive to mechanical loading by pulsating fluid flow (PFF) on osteogenic stimulation in vitro. We found that ATMSCs show a Bone Cell-like response to fluid shear stress as a result of PFF after the stimulation of osteogenic differentiation by 1,25-dihydroxyvitamin D3. PFF increased nitric oxide production, as well as upregulated cyclooxygenase-2, but not cyclooxygenase-1, gene expression in osteogenically stimulated AT-MSCs. These data suggest...
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the production of nitric oxide and prostaglandin e2 by primary Bone Cells is shear stress dependent
Journal of Biomechanics, 2001Co-Authors: Astrid D Bakker, Jenneke Kleinnulend, K Soejima, E H BurgerAbstract:Abstract Loading-induced flow of interstitial fluid through the lacuno-canalicular network is a likely signal for Bone Cell adaptive responses. However, the nature of the stimulus that activates the Cell is debated. Candidate stimuli include wall shear stress, streaming potentials, and chemotransport. We have addressed the nature of the flow-derived Cell stimulus by comparing variations in fluid transport with variations in wall shear stress, using nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) production as a parameter of Bone Cell activation. Adult mouse long Bone Cell cultures were treated for 15 min with or without pulsating fluid flow using the following regimes: Low PFF , mean flow rate 0.20 cm 3 /s, 3 Hz, shear stress 0.4±0.12 Pa; Medium PFF , 0.33 cm 3 /s, 5 Hz, 0.6±0.27 Pa; and High PFF , 0.63 cm 3 /s, 9 Hz, 1.2±0.37 Pa. In some Low PFF experiments, 2.8% neutral dextran (mol. wt. 4.98×10 4 ) was added to the flow medium to increase the viscosity, thereby increasing the wall shear stress 3-fold to a level similar of the High PFF stimulus, but without affecting streaming potentials or chemotransport. NO and PGE 2 production were stimulated by Low, Medium, and High PFF in a dose-dependent manner. Application of Low PFF using dextran-supplemented medium, enhanced both the NO and PGE 2 response by 3-fold, to a level mimicking the response to High PFF at normal viscosity. These results show that the production of NO and PGE 2 by Bone Cells can be enhanced in a dose-dependent manner by fluid flow of increasing wall shear stress. Therefore, the stimulus leading to NO and PGE 2 production is the flow-derived shear stress, and not streaming potentials or chemotransport.
M Knippenberg - One of the best experts on this subject based on the ideXlab platform.
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are affected by mechanical loading, which is thought to provoke a Cellular response via loading-induced flow of interstitial fluid. Adipose tissue is an easily accessible source of mesenchymal stem Cells for Bone tissue engineering, and is available in abundant amounts compared with Bone marrow. We studied whether adipose tissue-derived mesenchymal stem Cells (AT-MSCs) are responsive to mechanical loading by pulsating fluid flow (PFF) on osteogenic stimulation in vitro. We found that ATMSCs show a Bone Cell-like response to fluid shear stress as a result of PFF after the stimulation of osteogenic differentiation by 1,25-dihydroxyvitamin D3. PFF increased nitric oxide production, as well as upregulated cyclooxygenase-2, but not cyclooxygenase-1, gene expression in osteogenically stimulated AT-MSCs. These data suggest that AT-MSCs acquire Bone Cell-like responsiveness to pulsating fluid shear stress on 1,25-dihydroxyvitamin D3-induced osteogenic differentiation. ATMSCs might be able to perform Bone Cell-specific functions during Bone (re)modeling in vivo and, therefore, provide a promising new tool for Bone tissue engineering.
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are ...
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are affected by mechanical loading, which is thought to provoke a Cellular response via loading-induced flow of interstitial fluid. Adipose tissue is an easily accessible source of mesenchymal stem Cells for Bone tissue engineering, and is available in abundant amounts compared with Bone marrow. We studied whether adipose tissue-derived mesenchymal stem Cells (AT-MSCs) are responsive to mechanical loading by pulsating fluid flow (PFF) on osteogenic stimulation in vitro. We found that ATMSCs show a Bone Cell-like response to fluid shear stress as a result of PFF after the stimulation of osteogenic differentiation by 1,25-dihydroxyvitamin D3. PFF increased nitric oxide production, as well as upregulated cyclooxygenase-2, but not cyclooxygenase-1, gene expression in osteogenically stimulated AT-MSCs. These data suggest...
Ernesto Canalis - One of the best experts on this subject based on the ideXlab platform.
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further biochemical and molecular characterization of primary rat parietal Bone Cell cultures
Journal of Bone and Mineral Research, 2009Co-Authors: Thomas L Mccarthy, Michael Centrella, Ernesto CanalisAbstract:: Primary Bone Cell cultures are used widely to examine the regulation of Bone metabolism by growth factors and hormones. Characterization of this model system is now being conducted at the molecular level to define modulation of gene expression. Cells were obtained from rat parietal Bone by sequential collagenase digestions. Cell populations were evaluated for Bone-related products, including collagen isoform expression and mRNA levels, alkaline phosphatase activity, and osteocalcin production. Serum-deprived, confluent cultures of the first and second collagenase-released populations produced a lower percentage of total protein as collagen than the third, fourth, and fifth populations, while co-culturing the third through fifth populations resulted in the highest level. Collagen typing on SDS-polyacrylamide gels revealed an abundance of mature type I collagen in all Cell populations; type III collagen synthesis was undetectable by this method. This is in contrast to the presence of cytoplasmic mRNA for both type I and type III collagen in all Cell populations, suggesting post-transcriptional modulation of type III collagen synthesis. The expression of alkaline phosphatase and osteocalcin was highest in cultures of later released Cells, indicating that these Cell populations display phenotypic characteristics associated with Cells of the osteoblast lineage.
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the divalent strontium salt s12911 enhances Bone Cell replication and Bone formation in vitro
Bone, 1996Co-Authors: Ernesto Canalis, M Hott, Pascale Deloffre, Y Tsouderos, Pierre J MarieAbstract:Abstract In this study, we have determined the effect of the divalent strontium salt S12911 on Bone Cell replication and Bone formation in two culture systems. In the first series of experiments, half-calvariae of newborn rats were cultured with S12911 from 24 to 96 h and labeled with 3 H-thymidine for the last 6 h of culture or treated with S12911 for 24 h and labeled for 24 h with 3 H-proline 24–48 h after the removal of the agent. Calvariae were then processed for histomorphometry. S12911 at 10 −3 M increased the replication of preosteoblastic Cells by 30–50% after 24 h and by 60% after 96 h of treatment. This effect was specific, since the number of labeled osteoblasts and of periosteal Cells was not changed. A transient 24 h treatment with S12911 at 10 −3 M increased Bone formation 24 and 48 h after the removal of the agent. 3H -proline labeled surfaces and Bone formation rates were increased by 20%–35%. In the second series of experiments, sequential collagenase digestions were used to isolate Cell populations enriched in fibroblasts or osteoblasts (Ob) from 22 day fetal rat calvariae. Treatment with S12911 at 10 −3 M for 24 h enhanced DNA synthesis by three- to fourfold in Cell populations enriched in fibroblasts and preosteoblastic Cells. The effect was less pronounced and inconsistent in Ob Cells. S12911 at 10 −3 M for 24 h also increased collagen and non-collagen protein synthesis by 35% in Ob Cells. These data indicate that the divalent strontium salt S12911 enhances Bone Cell replication and Bone formation in vitro, an effect that may contribute to the previously reported effects of S12911 on trabecular Bone mass in vivo.
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Platelet-derived growth factor enhances Bone Cell replication, but not differentiated function of osteoblasts.
Endocrinology, 1994Co-Authors: Janet Hock, Ernesto CanalisAbstract:Platelet-derived growth factor (PDGF), a polypeptide mitogen, is a dimer composed of PDGF-AA and -BB chains. In rats, PDGF-BB is the prevalent circulating form, whereas in Bone, PDGF-AA is the isoform secreted by unstimulated normal Bone Cells. Although PDGF-BB increased DNA synthesis in fetal rat calvariae, the effects on collagen synthesis were small and inconsistent. To localize the Cells in the cranial periosteum that were responding to PDGF isoforms AA and BB, we cultured 21-day-old fetal rat calvariae to assess the effects of human recombinant PDGF-AA and -BB on Bone Cell replication and matrix formation. Changes were assessed using histomorphometry and autoradiography and correlated with effects on collagen synthesis and [3H]thymidine incorporation, using biochemical assays. PDGF-AA and -BB at 0.03-3.3 nM (1-100 ng/ml) for 24-72 h increased DNA synthesis by 1.5- to 3-fold; PDGF-BB was more potent than PDGF-AA. Although PDGF increased Cell replication in all Cell zones, the effects of both PDGF-AA and -BB were preferentially greater in the periosteal fibroblast zone, in which, at 3.3 nM, the labeling index (LI) was increased by 3-fold with AA and by 5-fold with BB. Cell replication of the Bone surface Cell (osteoblast) layer was increased by 2-fold with AA and by 2.5-fold with BB, whereas replication in the intermediate osteoprogenitor zone increased by 50% with AA and by 2.5-fold with BB. The increase in Cell replication was associated with a significant inhibition of Bone matrix-forming surfaces, with PDGF-BB being more potent at equivalent doses than -AA after 24-72 h of continuous treatment. Continuous or intermittent exposure to PDGF-AA or PDGF-BB for 24-72 h stimulated neither the rate of collagen synthesis nor organized Bone matrix formation in rat calvariae. In addition, PDGF-BB at 0.03-3.3 nM increased the number of osteoclasts and the percent eroded surface by 2- to 3-fold. Our studies show that PDGF-AA and -BB are mitogens affecting multiple Bone Cells, including those of the osteoblast and osteoclast lineage. Treatment with PDGF severely disrupted and inhibited Bone matrix formation, and there was no evidence to show that Cells incorporating [3H]thymidine differentiated into mature osteoblasts within the time frame of these experiments. In fetal rat calvaria, the most significant consequence of treatment with PDGF was the selective stimulation of fibroblast replication and function.
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Growth Factors and Cytokines in Bone Cell Metabolism
Annual review of medicine, 1991Co-Authors: Ernesto Canalis, Thomas L Mccarthy, Michael CentrellaAbstract:Growth factors regulate the growth and differentiated function of Cells. Skeletal Cells synthesize fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor, transforming growth factor beta, and additional cytokines. Some of the growth factors produced by Bone Cells primarily stimulate Bone Cell replication, whereas others also affect the differentiated function of the osteoblast. Skeletal growth factors also may play a role in the pathogenesis and therapy of metabolic Bone disease.
Paul I J M Wuisman - One of the best experts on this subject based on the ideXlab platform.
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are affected by mechanical loading, which is thought to provoke a Cellular response via loading-induced flow of interstitial fluid. Adipose tissue is an easily accessible source of mesenchymal stem Cells for Bone tissue engineering, and is available in abundant amounts compared with Bone marrow. We studied whether adipose tissue-derived mesenchymal stem Cells (AT-MSCs) are responsive to mechanical loading by pulsating fluid flow (PFF) on osteogenic stimulation in vitro. We found that ATMSCs show a Bone Cell-like response to fluid shear stress as a result of PFF after the stimulation of osteogenic differentiation by 1,25-dihydroxyvitamin D3. PFF increased nitric oxide production, as well as upregulated cyclooxygenase-2, but not cyclooxygenase-1, gene expression in osteogenically stimulated AT-MSCs. These data suggest that AT-MSCs acquire Bone Cell-like responsiveness to pulsating fluid shear stress on 1,25-dihydroxyvitamin D3-induced osteogenic differentiation. ATMSCs might be able to perform Bone Cell-specific functions during Bone (re)modeling in vivo and, therefore, provide a promising new tool for Bone tissue engineering.
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are ...
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are affected by mechanical loading, which is thought to provoke a Cellular response via loading-induced flow of interstitial fluid. Adipose tissue is an easily accessible source of mesenchymal stem Cells for Bone tissue engineering, and is available in abundant amounts compared with Bone marrow. We studied whether adipose tissue-derived mesenchymal stem Cells (AT-MSCs) are responsive to mechanical loading by pulsating fluid flow (PFF) on osteogenic stimulation in vitro. We found that ATMSCs show a Bone Cell-like response to fluid shear stress as a result of PFF after the stimulation of osteogenic differentiation by 1,25-dihydroxyvitamin D3. PFF increased nitric oxide production, as well as upregulated cyclooxygenase-2, but not cyclooxygenase-1, gene expression in osteogenically stimulated AT-MSCs. These data suggest...
C M Semeins - One of the best experts on this subject based on the ideXlab platform.
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are affected by mechanical loading, which is thought to provoke a Cellular response via loading-induced flow of interstitial fluid. Adipose tissue is an easily accessible source of mesenchymal stem Cells for Bone tissue engineering, and is available in abundant amounts compared with Bone marrow. We studied whether adipose tissue-derived mesenchymal stem Cells (AT-MSCs) are responsive to mechanical loading by pulsating fluid flow (PFF) on osteogenic stimulation in vitro. We found that ATMSCs show a Bone Cell-like response to fluid shear stress as a result of PFF after the stimulation of osteogenic differentiation by 1,25-dihydroxyvitamin D3. PFF increased nitric oxide production, as well as upregulated cyclooxygenase-2, but not cyclooxygenase-1, gene expression in osteogenically stimulated AT-MSCs. These data suggest that AT-MSCs acquire Bone Cell-like responsiveness to pulsating fluid shear stress on 1,25-dihydroxyvitamin D3-induced osteogenic differentiation. ATMSCs might be able to perform Bone Cell-specific functions during Bone (re)modeling in vivo and, therefore, provide a promising new tool for Bone tissue engineering.
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are ...
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adipose tissue derived mesenchymal stem Cells acquire Bone Cell like responsiveness to fluid shear stress on osteogenic stimulation
Tissue Engineering, 2005Co-Authors: M Knippenberg, Marco N Helder, Behrouz Zandieh Doulabi, C M Semeins, Paul I J M Wuisman, Jenneke KleinnulendAbstract:To engineer Bone tissue, mechanosensitive Cells are needed that are able to perform Bone Cell-specific functions, such as (re)modeling of Bone tissue. In vivo, local Bone mass and architecture are affected by mechanical loading, which is thought to provoke a Cellular response via loading-induced flow of interstitial fluid. Adipose tissue is an easily accessible source of mesenchymal stem Cells for Bone tissue engineering, and is available in abundant amounts compared with Bone marrow. We studied whether adipose tissue-derived mesenchymal stem Cells (AT-MSCs) are responsive to mechanical loading by pulsating fluid flow (PFF) on osteogenic stimulation in vitro. We found that ATMSCs show a Bone Cell-like response to fluid shear stress as a result of PFF after the stimulation of osteogenic differentiation by 1,25-dihydroxyvitamin D3. PFF increased nitric oxide production, as well as upregulated cyclooxygenase-2, but not cyclooxygenase-1, gene expression in osteogenically stimulated AT-MSCs. These data suggest...