Skip to Content
Merck
  • Mechanical stimulation of human tendon stem/progenitor cells results in upregulation of matrix proteins, integrins and MMPs, and activation of p38 and ERK1/2 kinases.

Mechanical stimulation of human tendon stem/progenitor cells results in upregulation of matrix proteins, integrins and MMPs, and activation of p38 and ERK1/2 kinases.

BMC molecular biology (2015-04-17)
Cvetan Popov, Martina Burggraf, Ludwika Kreja, Anita Ignatius, Matthias Schieker, Denitsa Docheva
ABSTRACT

Tendons are dense connective tissues subjected periodically to mechanical stress upon which complex responsive mechanisms are activated. These mechanisms affect not only the development of these tissues but also their healing. Despite of the acknowledged importance of the mechanical stress for tendon function and repair, the mechanotransduction mechanisms in tendon cells are still unclear and the elucidation of these mechanisms is a key goal in tendon research. Tendon stem/progenitor cells (TSPC) possess common adult stem cell characteristics, and are suggested to actively participate in tendon development, tissue homeostasis as well as repair. This makes them an important cell population for tendon repair, and also an interesting research target for various open questions in tendon cell biology. Therefore, in our study we focused on TSPC, subjected them to five different mechanical protocols, and investigated the gene expression changes by using semi-quantitative, quantitative PCR and western blotting technologies. Among the 25 different genes analyzed, we can convincingly report that the tendon-related genes - fibromodulin, lumican and versican, the collagen I-binding integrins - α1, α2 and α11, the matrix metalloproteinases - MMP9, 13 and 14 were strongly upregulated in TSPC after 3 days of mechanical stimulation with 8% amplitude. Molecular signaling analyses of five key integrin downstream kinases suggested that mechanical stimuli are mediated through ERK1/2 and p38, which were significantly activated in 8% biaxial-loaded TSPC. Our results demonstrate the positive effect of 8% mechanical loading on the gene expression of matrix proteins, integrins and matrix metalloproteinases, and activation of integrin downstream kinases p38 and ERK1/2 in TSPC. Taken together, our study contributes to better understanding of mechanotransduction mechanisms in TPSC, which in long term, after further translational research between tendon cell biology and orthopedics, can be beneficial to the management of tendon repair.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Bicinchoninic acid disodium salt hydrate, ≥98% (HPLC)
Pricing and availability is not currently available.
Supelco
4-tert-Octylphenol monoethoxylate solution, 10 μg/mL in acetone, analytical standard
Pricing and availability is not currently available.
Supelco
DL-Dithiothreitol solution, 1 M in H2O
Pricing and availability is not currently available.
Sigma-Aldrich
DL-Dithiothreitol solution, BioUltra, for molecular biology, ~1 M in H2O
Pricing and availability is not currently available.
Indomethacin, European Pharmacopoeia (EP) Reference Standard
Pricing and availability is not currently available.
Supelco
Indomethacin, Pharmaceutical Secondary Standard; Certified Reference Material
Pricing and availability is not currently available.
Dexamethasone for peak identification, European Pharmacopoeia (EP) Reference Standard
Pricing and availability is not currently available.
Sigma-Aldrich
Glycerol solution, 83.5-89.5% (T)
Pricing and availability is not currently available.
Sigma-Aldrich
Indomethacin, 98.5-100.5% (in accordance with EP)
Pricing and availability is not currently available.
Sigma-Aldrich
Indomethacin, meets USP testing specifications
Pricing and availability is not currently available.
Sigma-Aldrich
3-Isobutyl-1-methylxanthine, ≥99% (HPLC), powder
Pricing and availability is not currently available.
Sigma-Aldrich
3-Isobutyl-1-methylxanthine, BioUltra, ≥99%
Pricing and availability is not currently available.
USP
Indomethacin, United States Pharmacopeia (USP) Reference Standard
Pricing and availability is not currently available.
Supelco
Glycerin, Pharmaceutical Secondary Standard; Certified Reference Material
Pricing and availability is not currently available.
Supelco
Dexamethasone, VETRANAL®, analytical standard
Pricing and availability is not currently available.
Sigma-Aldrich
Dexamethasone, tested according to Ph. Eur.
Pricing and availability is not currently available.
Sigma-Aldrich
Phenylacetic acid, 99%
Pricing and availability is not currently available.
Sigma-Aldrich
1,2-Diaminocyclohexane, mixture of cis and trans, 99%
Pricing and availability is not currently available.
Sigma-Aldrich
Glycerol, tested according to Ph. Eur., anhydrous
Pricing and availability is not currently available.
Sigma-Aldrich
Dexamethasone, meets USP testing specifications
Pricing and availability is not currently available.
Sigma-Aldrich
Dexamethasone, ≥98% (HPLC), powder
Pricing and availability is not currently available.
Sigma-Aldrich
Dexamethasone, powder, γ-irradiated, BioXtra, suitable for cell culture, ≥80% (HPLC)
Pricing and availability is not currently available.
Dexamethasone, European Pharmacopoeia (EP) Reference Standard
Pricing and availability is not currently available.
Sigma-Aldrich
Phenylacetic acid, ≥99%, FCC, FG
Pricing and availability is not currently available.
Sigma-Aldrich
Glycerol, ReagentPlus®, ≥99.0% (GC)
Pricing and availability is not currently available.
Sigma-Aldrich
Glycerol, ACS reagent, ≥99.5%
Pricing and availability is not currently available.
Supelco
Glycerol, analytical standard
Pricing and availability is not currently available.
Supelco
Dexamethasone, Pharmaceutical Secondary Standard; Certified Reference Material
Pricing and availability is not currently available.
USP
Dexamethasone, United States Pharmacopeia (USP) Reference Standard
Pricing and availability is not currently available.
Dexamethasone, British Pharmacopoeia (BP) Assay Standard
Pricing and availability is not currently available.