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Cyclic stretch enhances gap junctional communication between osteoblastic cells

K Ziambaras1, F Lecanda, T H Steinberg

  • 1Department of Internal Medicine, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|March 12, 1998
PubMed
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Mechanical loading is crucial for bone health. This study shows that cyclic stretch enhances gap junctional communication in osteoblasts by altering connexin43 protein localization, not its expression.

Area of Science:

  • Bone biology
  • Cellular communication
  • Mechanobiology

Background:

  • Mechanical loading is vital for maintaining skeletal integrity.
  • Gap junctions facilitate direct intercellular communication in bone cells.
  • Osteoblasts respond to mechanical stimuli, but their intercellular communication under stretch is not fully understood.

Purpose of the Study:

  • To investigate whether mechanical stretch modulates direct intercellular communication in osteoblasts.
  • To determine the role of connexin43 (Cx43) in stretch-induced changes in osteoblast communication.

Main Methods:

  • Utilized a novel "parachute assay" to measure dye diffusion across gap junctions without plasma membrane disruption.
  • Applied cyclic stretch to ROS 17/2.8 and UMR 106-01 osteoblast cell lines.

Related Experiment Videos

  • Assessed connexin43 (Cx43) mRNA levels, Cx43 protein phosphorylation, and its cellular localization via immunostaining.
  • Investigated the effect of the gap junction inhibitor heptanol.

    • Main Results:

    • Cyclic stretch significantly increased dye coupling in well-coupled ROS 17/2.8 cells (56.5% at 2h, 30.4% at 24h).
    • A smaller increase in dye diffusion was observed in poorly coupled UMR 106-01 cells (12.4%).
    • Stretch-induced communication enhancement was blocked by heptanol.
    • Steady-state Cx43 mRNA levels remained unchanged, but phosphorylated Cx43 protein increased, with enhanced membrane localization in stretched cells.

    Conclusions:

    • Cyclic mechanical stretch enhances gap junctional communication between osteoblastic cells.
    • This enhancement is mediated by the modulation of connexin43 (Cx43) intracellular localization and phosphorylation, rather than changes in Cx43 gene expression.
    • Findings highlight a novel mechanism by which mechanical forces influence bone cell communication and potentially skeletal integrity.