ABSTRACT
Orthodontic tooth movement is a dynamic process, which includes bone resorption on the pressure side and osteogenesis on the tension side. Bone mesenchymal stem cells (BMSCs), which are force-sensitive cells, have potentials for differentiation into cells with various types. Their biological characteristics can change functionally according to the appropriate stimulation in vitro, in order to reach the optimal demand of the stimulation. Many signal pathways are involved in osteogenesis. Signal transducers and activators of transcription 3 (STAT3) is a ubiquitously expressed transcription factor, mediating cell proliferation, differentiation, survival, apoptosis and cellular immunity. It has been reported that STAT3 can regulate the differentiation process of BMSCs into osteoblasts. This paper summarizes the recent progress about effect of STAT3 on bone differentiation of BMSCs and the possible mechanism.
ABSTRACT
Orthodontic tooth movement is a dynamic process,which includes bone resorption on the pressure side and osteogenesis on the tension side.Bone mesenchymal stem cells (BMSCs),which are force-sensitive cells,have potentials for differentiation into cells with various types.Their biological characteristics can change functionally according to the appropriate stimulation in vitro,in order to reach the optimal demand of the stimulation.Many signal pathways are involved in osteogenesis.Signal transducers and activators of transcription 3 (STAT3) is a ubiquitously expressed transcription factor,mediating cell proliferation,differentiation,survival,apoptosis and cellular immunity.It has been reported that STAT3 can regulate the differentiation process of BMSCs into osteoblasts.This paper summarizes the recent progress about effect of STAT3 on bone differentiation of BMSCs and the possible mechanism.
ABSTRACT
Orthodontic tooth movement is a dynamic process,which includes bone resorption on the pressure side and osteogenesis on the tension side.Bone mesenchymal stem cells (BMSCs),which are force-sensitive cells,have potentials for differentiation into cells with various types.Their biological characteristics can change functionally according to the appropriate stimulation in vitro,in order to reach the optimal demand of the stimulation.Many signal pathways are involved in osteogenesis.Signal transducers and activators of transcription 3 (STAT3) is a ubiquitously expressed transcription factor,mediating cell proliferation,differentiation,survival,apoptosis and cellular immunity.It has been reported that STAT3 can regulate the differentiation process of BMSCs into osteoblasts.This paper summarizes the recent progress about effect of STAT3 on bone differentiation of BMSCs and the possible mechanism.
ABSTRACT
Objective To study the remodeling of alveolar bone and change in expression of forkhead box O1 (FOXO1) during orthodontic tooth movement (OTM) in rat, so as to preliminarily investigate the role of FOXO1 in alveolar bone remodeling induced by orthodontic force. Methods The rat OTM models were established and the left maxillary 1st molars were moved with force of 50 g. The rats were executed on the 1st, 3rd and 7th day of OTM, respectively. HE staining and immunohistochemical staining were used to observe the remodeling of alveolar bone in the inter-radicular region of the 1st molars and expression of FOXO1 at different time points during OTM. Results The 1st molars were constantly moved mesially under orthodontic force. There were more osteoclasts in the alveolar bone of OTM group than that in non-OTM group, and the osteoclasts on the 3rd day of OTM showed the highest activity. The number of active osteoblasts gradually increased in the inter-radicular region of alveolar bone under orthodontic force, with the enhanced osteoblast activity. Expression of FOXO1 in OTM group was elevated compared with non-OTM group. Most osteoblasts in alveolar bone during OTM were FOXO1 positive, and the expression of FOXO1 was gradually increased with the number of osteoblasts increasing. Conclusions Orthodontic force induces bone remodeling of alveolar bone in the inter-radicular region during OTM, and the change in FOXO1 expression may be related to alveolar bone remodeling during OTM.
ABSTRACT
Objective To study the effect of continuous tensile stress on expression of Forkhead box protein O1 (FoxO1) in MC3T3-E1 cells in vitro during osteogenic differentiation, and explore the role of FoxO1 in the mechanism of continuous tensile stress induced-osteogenic differentiation. Methods MC3T3-E1 cells were seeded and applied with tensile stress at the frequency of 1 Hz and amplitude of 10% by FX-4000TTM mechanical loading system. MC3T3-E1 cells were divided into control, 1 h, 4 h, 6 h, 12 h, 24 h, 48 h, 72 h group, respectively, according to the time subjected to the tensile stress. Alkaline phosphatase (ALP) staining, real-time PCR, Western blotting and immunofluorescence were applied to detect the effects of continuous tensile stress on osteogenesis ability of MC3T3-E1 cells, mRNA and protein expression of FoxO1, and allocation of FoxO1 in MC3T3-E1 cells. Results (1) Continuous tensile stress could promote the osteogenic differentiation of MC3T3-E1 cells. Compared with the control group, the mRNA expression of ALP increased significantly at 24 h, 48 h, and the mRNA expression level of osteocalcin (OCN) reached the peak value at 72 h, which was significantly higher than that in the control group. The mRNA expression of runt-related transcription factor-2 (Runx2) significantly increased at 4 h as compared to the control group, and Runx2 protein level changed accordingly. The ALP staining results of the stress group and control group were significantly different. (2) Continuous tensile stress could increase mRNA and protein expression of FoxO1. The mRNA expression of FoxO1 markedly increased at 24 h, and its protein expression significantly elevated at 12 h. (3) FoxO1 was expressed in the nucleus and cytoplasm at 6 h, and then significantly increased in the cytoplasmat at 24 h. Conclusions 10% continuous tensile stress can stimulate the osteogenic differentiation of MC3T3-E1 cells, up-regulate the mRNA and protein expression of FoxO1 and change the allocation of FoxO1 in MC3T3-E1 cells. The investigation on the change rules of FoxO1 expression and allocation under mechanical stimulation will provide the experimental basis for studying the role of FoxO1 in mechanical stimulation.
ABSTRACT
Objective To evaluate differences in genes expression of rat bone marrow stromal cells (rBMSCs) under continuous mechanical strain by gene microarray technology．Methods rBMSCs were isolated and cultured in vitro. Continuous stresses with amplitude of 10% and frequency of 1 Hz were applied on rBMSCs for 6 hours by Flexercell mechanical loading system to investigate rBMSC gene expression profiles, and quantitative PCR was used to verify gene expression changes related to osteoblastic differentiation. Results Compared with the control group, 1 244 differentially expressed genes were found in mechanical loading group, among which 793 genes were up-regulated, while 451 genes were down-regulated．GO (gene ontology) analysis suggested that differentially expressed genes were mainly involved in multicellular organismal development, cell differentiation, chemotaxis, cell adhesion and so on. Four signaling pathways as Notch, Wnt, FGF and IGF might participate in the regulation of stress-induced osteoblastic differentiation. PCR validation results were consistent with the gene chip results. Conclusions Mechanical stress could induce osteoblastic differentiation of the BMSCs, while several differentially expressed genes screened by gene microarray may attribute to this process.
ABSTRACT
Objective To study the effect of continuous strain on the proliferation and osteogenic differentiation of rat bone marrow stromal cells(BMSCs) in vitro. Methods Rat BMSCs were obtained from adult female Sprague-Dawley rats (3-month old), and purified by full-blood attachment culture. BMSCs between passage 3—5 were seeded on Flexercell mechanical loading system(10%, 1 Hz), and divided into 1 h group, 6 h group, 12 h group, 24 h group, 48 h group, respectively, according to the time subjected to strain. Effects of continuous strain on the morphology, proliferation and osteogenic differentiation of BMSCs were observed and analyzed. Results (1) Compared with the control group, cells subjected to 10% strain showed the particular orientation. Their alignment elongated mostly in the direction perpendicular to the strain axis in a time-dependent manner. (2)10% continuous strain could significantly decrease the proliferation of BMSCs. (3) Continuous strain could increase mRNA expression of ALP, COLⅠand Runx2 in a time-dependent manner. Compared with the control group, mRNA expression of ALP was increased significantly at 24 h, COLⅠat 24 h and 48 h, and Runx2 at 6 h. mRNA expression of osteocalcin (OC) ascended greatly in the beginning, but went down gradually and was significantly lower than that of control at 48 h（P＜0.05）. (4) Continuous strain could induce an increase in Runx2 protein level. A sharp increase in Runx2 protein was observed at 6 h(P＜0.05) , then Runx2 protein level decreased slowly with its mRNA expression being significantly lower than that of control at 24 h（P＜0.05） Conclusions Continuous strain could induce rat BMSCs to orient in an orderly manner, suppress its proliferation activity, but stimulate the osteoblastic differentiation at the early stage.
ABSTRACT
Objective To investigate the effect of intermittent tensile strain on the proliferation and osteogenic differentiation of rBMSCs (rat bone mesenchymal stem cells). Methods Intermittent tensile strain was applied on rBMSCs in vitro by Flexcell 4 000 Tension System (10% elongation amplitude, 0.5 Hz, twice every day, 4 h every time), then effects of the strain after 1, 3, 5, 7 d on cell morphology, cell proliferation, and the relative expression of Cbfα1（core binding factor α1），ALP and collagen I mRNA as well as Cbfα1 protein were measured. Results Intermittent tensile strain slowed the proliferation of rBMSCs from the first day to the seventh day. The relative expression of ALP and collagen I mRNA increased by 3~6 times from the third day（P＜0.05）, meanwhile the expression of Cbfα1 mRNA and protein was up-regulated under the mechanical stimulation. Conclusions Mechanical stretch plays an important role in the proliferation and differentiation of rBMSC, and approprite intermittent tensile strain can slow the proliferation of rBMSC and promot its osteogenic differentiation.
ABSTRACT
Mechanical stimulation plays an important role in the normal metabolism and reorganization of bone. Many kinds of stress sensitive cells, including osteoblasts, can perceive and transduce the mechanical signals. As the fibrous framework throughout a cell, cytoskeleton as well as extracellular matrix and integrin is one of the critical components in mechanotransduction. Mechanical stimulation can induce the rearrangement of the cytoskeleton, and the signals are transduced and transformed by the second messagers, finally resulting in the changes of gene expression.The family of Rho, protein kinase C and focal adhesion kinase are the main messages involved in this process. This paper summarizes the recent advances about the effects and possible mechanism of mechanical stimulation on osteoblast cytoskeleton.