J Bone Metab.  2019 Aug;26(3):179-191. 10.11005/jbm.2019.26.3.179.

Mechanical and Mechanosensing Properties of Tumor Affected Bone Cells Were Inhibited via PI3K/Akt Pathway

Affiliations
  • 1Division of Mechanical and Biomedical Engineering, Ewha Womans University, Seoul, Korea. tlee@ewha.ac.kr

Abstract

BACKGROUND
Osteolytic metastasis is a common destructive form of metastasis, in which there is an increased bone resorption but impaired bone formation. It is hypothesized that the changed mechanical properties of tumor affected bone cells could inhibit its mechanosensing, thus contributing to differences in bone remodeling.
METHODS
Here, atomic force microscopy indentation on primary bone cells exposed to 50% conditioned medium from Walker 256 (W) carcinoma cell line or its adaptive tumor (T) cells was carried out. Nitric oxide levels of bone cells were monitored in response to low-magnitude, high-frequency (LMHF) vibrations.
RESULTS
A stronger sustained inhibitive effect on bone cell viability and differentiation by T cells as compared to that of its cell line was demonstrated. This could be attributed to the higher levels of transforming growth factor-β1 (TGF-β1) in the T-conditioned medium as compared to W-conditioned medium. Bone cell elastic moduli in W and T-groups were found to decrease significantly by 61.0% and 69.6%, respectively compared to control and corresponded to filamentous actin changes. Nitric oxide responses were significantly inhibited in T-conditioned group but not in W-conditioned group.
CONCLUSIONS
It implied that a change in cell mechanical properties is not sufficient as an indicator of change in mechanosensing ability. Moreover, inhibition of phosphoinositide 3-kinase/Akt downstream signaling pathway of TGF-β1 alleviated the inhibition effects on mechanosensing in T-conditioned cells, further suggesting that growth factors such as TGF-β could be good therapeutic targets for osteoblast treatment.

Keyword

Bone metastasis; Bone neoplasms; Elastic modulus; Mechanosensing; Nitric oxide

MeSH Terms

Actins
Bone Neoplasms
Bone Remodeling
Bone Resorption
Cell Line
Cell Survival
Culture Media, Conditioned
Elastic Modulus
Intercellular Signaling Peptides and Proteins
Microscopy, Atomic Force
Neoplasm Metastasis
Nitric Oxide
Osteoblasts
Osteogenesis
Sensitivity Training Groups
T-Lymphocytes
Vibration
Walkers
Actins
Culture Media, Conditioned
Intercellular Signaling Peptides and Proteins
Nitric Oxide
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