Mechanical load modulates chondrogenesis of human mesenchymal stem cells through the TGF-β pathway

نویسندگان

  • Zhen Li
  • Laszlo Kupcsik
  • Shan-Jing Yao
  • Mauro Alini
  • Martin J Stoddart
چکیده

This study investigated the effect of mechanical load on human mesenchymal stem cell (hMSC) differentiation under different exogenous transforming growth factor-beta1 (TGF-beta(1)) concentrations (0, 1 or 10 ng/ml).The role of the TGF-beta signalling pathway in this process was also studied. Human MSCs were seeded into fibrin-biodegradable polyurethane scaffolds at a cell density of 5 x 10(6) cells per scaffold and stimulated using our bioreactor. One hour of surface motion superimposed on cyclic compression was applied once a day over seven consecutive days. Scaffolds were analysed for gene expression, DNA content and glycosaminoglycan amount. Addition of TGF-beta(1) in the culture medium was sufficient to induce chondrogenesis of hMSCs. Depending on the TGF-beta(1) concentration of the culture medium, mechanical load stimulated chondrogenesis of hMSCs compared to the unloaded scaffolds, with a much stronger effect on gene expression at lower TGF-beta(1) concentrations. With TGF-beta(1) absent in the culture medium, mechanical load stimulated gene transcripts and protein synthesis of TGF-beta(1) and TGF-beta(3). TGF-beta type I receptor inhibitor LY364947 blocked the up-regulation on TGF-beta(1) and TGF-beta(3) production stimulated by mechanical load, and also blocked the chondrogenesis of hMSCs. Taken together, these findings suggest that mechanical load promotes chondrogenesis of hMSCs through TGF-beta pathway by up-regulating TGF-beta gene expression and protein synthesis.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

TGF-β1 enhanced myocardial differentiation through inhibition of the Wnt/β-catenin pathway with rat BMSCs

Objective(s): To investigate and test the hypotheses that TGF-β1 enhanced myocardial differentiation through Wnt/β-catenin pathway with rat bone marrow mesenchymal stem cells (BMSCs).Materials and Methods: Lentiviral vectors carrying the TGF-β1 gene were transduced into rat BMSCs firstly. Then several kinds of experimental methods were u...

متن کامل

Induction of Chondrogenic Differentiation of Human Adipose-Derived Stem Cells with TGF-β3 in Pellet Culture System

Objective Adult stem cells which are derived from different tissues, with their unique abilities to self-renew and differentiate into various phenotypes have the potential for cell therapy and tissue engineering. Human adipose tissue is an appropriate source of mesenchymal stem cells with wide differentiation potential for tissue engineering research. In this study isolated stem cells from hum...

متن کامل

Glucose Effect of Pre-differentiation Culture on Chondrogenesis of Human Mesenchymal Stem Cells

hMSCs maintained in low-glucose and high-glucose DMEM for different cell passages. Low-glucose-maintained cells expressed up-regulated collagen types II and IX in both P6 and P9 cells. Fig 2. Gene expression of the TGF-β signaling molecules, TGF-β1, and TGF-β receptors 1 (TGFβR1) and 2 (TGFβR2) before and two hours after medium change. The expression levels were similar between lowand highgluco...

متن کامل

Small Molecule-BIO Accelerates and Enhances Marrow-Derived Mesenchymal Stem Cell in Vitro Chondrogenesis

Background: Hyaline cartilage defects exhibit a major challenge in the field of orthopedic surgery owing to its limited repair capacity. On the other hand, mesenchymal stem cells (MSCs) are regarded as potent cells with a property of cartilage regeneration. We aimed to optimize marrow-derived MSC chondrogenic culture using a small bioactive molecule referred to as BIO. Methods: MSCs from the ma...

متن کامل

Comparison of TGF-β and Nitric oxide production by adipose-derived mesenchymal stem cells between healthy pregnant and preeclamptic women

Background: Preeclampsia is one of the most common complications of pregnancy that occurs after the 20th weeks of pregnancy.The pathophysiology of this disease is not exactly known. Transforming Growth Factor-beta (TGF-β) and Nitric Oxide (NO) are thekey regulatory factors secreted by Mesenchymal stem Cells (MSCs). Objectives: The aim of the present study was to evaluate the TGF-β and NO secret...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 14  شماره 

صفحات  -

تاریخ انتشار 2010