Identifying the mediators of mechanotransduction between bone cells

A problem presented at the Canadian MMSG Toronto 2009.

Presented by:
Prof Svetlana Komarova (Faculty of Dentistry, McGill University)
P Buono, SV Komarova, R Miura, A Pan, MC Pugh, S Qazi, D Wall, T Wright

Problem Description

Sensitivity to mechanical forces is one of the critical properties of many tissues in the body, including bone. Bone mass and architecture are regulated by mechanical forces, resulting in increase in bone mass in response to excessive loading and decrease in bone mass in the absence of physical activity. Bone in adult organism is constantly remodelled by the cooperative action of two cell types. Different types of mechanical forces lead to cell membrane deformation, which is thought to be the triggering event for significant downstream cellular response to mechanical stimulation. In addition, some evidence suggests that cells experiencing mechanical forces may communicate their status to remote cells which are not under direct influence of these forces.

The objective of our study is to assess the means by which mechanical stimulation is communicated among bone cells. From experimental results, is it possible to estimate the molecular weight of a second mediator? Can we be certain that there is only 1 mediator released? If not, is it possible to assess if 2 (or 3?) mediators act concurrently (both released from the primary, stimulated cells) or sequentially (first signal is released from the stimulated cell, acts on the next neighbour, which in turn releases the second signal which acts on the more distant cells)?

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Study Group Report

Models were proposed to account for ATP degradation and diffusion dynamics, and also osteoclast mediator propagation. Folloing comparison with the available experimental data, the following conclusions were drawn:

  1. A mediator is released from a single source cell.
  2. The response to the mediator changes with distance.
  3. The value of the apparent diffusion coefficient increases with distance.
  4. A plausible proposed mechanism is that ATP is released and degrades to ADP.
  5. Future experiments are required to confirm that ATP is the mediator as suggested.

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