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

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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.

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Acknowledgments

We would like to thank our technician Svetlana Penn for technical assistance. This research was supported by the Israel Science Foundation (Grant No. 292/07) and by the United States–Israel Binational Science Foundation (BSF) (Grant No. 2011393).

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  1. Adi Reich

    Present address: Bone and Extracellular Matrix Branch, National Institute of Child Health and Human Development, Bethesda, 20892-1830, MD, USA

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  1. Institute of Biochemistry and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University, P.O. Box 12, 76100, Rehovot, Israel

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

  2. Department of Prosthodontics, Oral Biology and Tissue Regeneration Work Group, Medical Faculty, Georg-August-University, 37075, Goettingen, Germany

    Nicolai Miosge

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Y. Rais and A. Reich are these authors contributed equally to the paper.

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Rais, Y., Reich, A., Simsa-Maziel, S. et al. The growth plate’s response to load is partially mediated by mechano-sensing via the chondrocytic primary cilium. Cell. Mol. Life Sci. 72, 597–615 (2015). https://doi.org/10.1007/s00018-014-1690-4

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