近期,，國(guó)際學(xué)術(shù)期刊Journal of Cellular Physiology在線發(fā)表了中科院上海生命科學(xué)研究院/上海交大醫(yī)學(xué)院健康所、中科院干細(xì)胞生物學(xué)重點(diǎn)實(shí)驗(yàn)室戴尅戎院士研究組的研究成果Continuous Cyclic Mechanical Tension Inhibited Runx2 Expression in Mesenchymal Stem Cells through RhoA-ERK1/2 Pathway,。本項(xiàng)研究發(fā)現(xiàn),，連續(xù)施加周期性拉應(yīng)力對(duì)于間充質(zhì)干細(xì)胞成骨分化有明顯的抑制作用，同時(shí)首次揭示這一抑制過(guò)程則是通過(guò)RhoA-ERK1/2-Runx2通路介導(dǎo),。
間充質(zhì)干細(xì)胞（Mesenchymal Stem Cells,，MSCs）具有多向分化的潛能，即在特定的誘導(dǎo)條件下可分化為骨,、軟骨,、脂肪、肌腱,、肌肉以及骨髓基質(zhì)等多種組織細(xì)胞,，在臨床治療以及組織工程中具有廣闊的應(yīng)用前景,。因此，探究MSCs分化的調(diào)控機(jī)制成為該領(lǐng)域研究的焦點(diǎn),。力學(xué)刺激作為一種物理性的刺激形式,，是細(xì)胞微環(huán)境中細(xì)胞命運(yùn)調(diào)控的重要因素,，也成為研究MSCs分化調(diào)控機(jī)制的重要手段,，而關(guān)注力學(xué)刺激如何調(diào)控MSCs向骨方向分化方面的研究，對(duì)進(jìn)一步揭示細(xì)胞微環(huán)境對(duì)MSCs命運(yùn)調(diào)控機(jī)制的研究將提供有價(jià)值的理論依據(jù),，也為MSCs的臨床治療與組織工程奠定基礎(chǔ),。
戴尅戎院士課題組的石玉博士研究生等科研人員應(yīng)用國(guó)際上先進(jìn)的細(xì)胞力學(xué)刺激儀器（Flexcell 4000+系統(tǒng)），對(duì)MSCs進(jìn)行連續(xù)周期性拉應(yīng)力刺激（Continuous Cyclic Mechanical Tension,，CCMT）,，結(jié)果發(fā)現(xiàn)：MSCs向成骨分化的主要標(biāo)記包括核心結(jié)合因子（Runt-related 2，Runx2）,、骨橋蛋白（osteopontin,，OPN）、堿性磷酸酶（Alkaline phosphatase,，ALP）,、1型膠原(Collagen Type 1，COL-1)等表達(dá)明顯降低,，且這種連續(xù)周期性拉應(yīng)力可抑制一類重要的小GTP結(jié)合蛋白——RhoA的活化,，外源性地激活RhoA可以解除力學(xué)刺激對(duì)成骨分化的抑制作用。進(jìn)一步的研究發(fā)現(xiàn),，RhoA活化可影響下游重要的MAPK-ERK1/2的磷酸化水平,，進(jìn)而調(diào)節(jié)Runx2的表達(dá)水平，最終抑制了間充質(zhì)干細(xì)胞向成骨分化,。
該項(xiàng)研究為應(yīng)用力學(xué)刺激進(jìn)行骨再生,、骨塑性的臨床治療提供了重要的理論依據(jù)。
該項(xiàng)工作得到了國(guó)家科技部,、國(guó)家基金委,、中國(guó)科學(xué)院以及上海市科委經(jīng)費(fèi)的支持。（生物谷Bioon.com）
生物谷推薦原文出處：
Journal of Cellular Physiology DOI: 10.1002/jcp.22551
Continuous cyclic mechanical tension inhibited Runx2 expression in mesenchymal stem cells through RhoA-ERK1/2 pathway
Yu Shi1, Huiwu Li2, Xiaoling Zhang1, Yujie Fu1, Yan Huang1, Pauline Po Yee Lui3,4,5, Tingting Tang2, Kerong Dai1,2,*
Keywords:continuous cyclic mechanical tension (CCMT);mesenchymal stem cell;osteogenesis;RhoA;ERK1/2-Runx2
Abstract
Tensile load is known to regulate the osteogenesis of mesenchymal stem cells (MSCs) and osteogenic progenitors; therefore it is widely used in clinical treatment and tissue engineering. Meanwhile, in vitro, both published studies and our lab data demonstrate that the application of intermittent tensile loading which stimulates cells several minutes or hours each day for several days has promoted the osteogenic differentiation of MSCs. Whereas, for clinic trails, it is important to know accurately how and how long mechanical tension should be applied. Hence, it is necessary to investigate different kinds of mechanical tension on osteogenesis of MSCs. Until now, during the osteogenesis, there has been no research on the effect of continuous cyclic mechanical tension (CCMT) which provides continuous stimulation throughout the study period. We firstly figure out CCMT inhibiting the expression of osteogenic genes such as key transcription factor Runx2. It is known that RhoA regulates cell differentiation in response to mechanical stimuli. MAPK signaling acts as a downstream effector of RhoA. So, we ask in MSCs, if CCMT regulates the osteogenic master gene Runx2 through RhoA-ERK1/2 pathway. And then, we find out there is a decrease in RhoA activity after CCMT stimulation. Pre-treatment of CCMT-loaded MSCs with LPA, a RhoA activator, restores ALP activity and significantly rescues Runx2 expression, while pre-treatment with C3 toxin, a RhoA inhibitor, further decreases the activity of ALP and down-regulates the expression of Runx2. Following results indicate that the inhibition of Runx2 expression after CCMT stimulation is mediated by RhoA-ERK1/2 pathway. J. Cell. Physiol. ? 2010 Wiley-Liss, Inc.
