The growth plate's response to load is partially mediated by mechano-sensing via the chondrocytic primary cilium

Yoach Rais, Adi Reich, Stav Simsa-Maziel, Maya Moshe, Anna Idelevich, Tal Kfir, Nicolai Miosge, Efrat Monsonego-Ornan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Mechanical load plays a significant role in bone and growth-plate development. Chondrocytes sense and respond to mechanical stimulation; however, the mechanisms by which those signals exert their effects are not fully understood. The primary cilium has been identified as a mechano-sensor in several cell types, including renal epithelial cells and endothelium, and accumulating evidence connects it to mechano-transduction in chondrocytes. In the growth plate, the primary cilium is involved in several regulatory pathways, such as the non-canonical Wnt and Indian Hedgehog. Moreover, it mediates cell shape, orientation, growth, and differentiation in the growth plate. In this work, we show that mechanical load enhances ciliogenesis in the growth plate. This leads to alterations in the expression and localization of key members of the Ihh-PTHrP loop resulting in decreased proliferation and an abnormal switch from proliferation to differentiation, together with abnormal chondrocyte morphology and organization. Moreover, we use the chondrogenic cell line ATDC5, a model for growth-plate chondrocytes, to understand the mechanisms mediating the participation of the primary cilium, and in particular KIF3A, in the cell's response to mechanical stimulation. We show that this key component of the cilium mediates gene expression in response to mechanical stimulation.

Original languageAmerican English
Pages (from-to)597-615
Number of pages19
JournalCellular and Molecular Life Sciences
Volume72
Issue number3
DOIs
StatePublished - Feb 2015

Bibliographical note

Publisher Copyright:
© 2014 Springer Basel.

Keywords

  • Aggrecan
  • Cartilage
  • Collagen
  • IFT88
  • Osteopontin
  • PKD

Fingerprint

Dive into the research topics of 'The growth plate's response to load is partially mediated by mechano-sensing via the chondrocytic primary cilium'. Together they form a unique fingerprint.

Cite this