caa a22 4500 606175903 CHVBK 20210128100745.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00018-014-1690-4 doi (NATIONALLICENCE)springer-10.1007/s00018-014-1690-4 The growth plate's response to load is partially mediated by mechano-sensing via the chondrocytic primary cilium [Elektronische Daten] [Yoach Rais, Adi Reich, Stav Simsa-Maziel, Maya Moshe, Anna Idelevich, Tal Kfir, Nicolai Miosge, Efrat Monsonego-Ornan] 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. Springer Basel, 2014 Collagen nationallicence Aggrecan nationallicence IFT88 nationallicence Osteopontin nationallicence PKD nationallicence Cartilage nationallicence Rais Yoach 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 aut Reich Adi 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 aut Simsa-Maziel Stav 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 aut Moshe Maya 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 aut Idelevich Anna 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 aut Kfir Tal 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 aut Miosge Nicolai Department of Prosthodontics, Oral Biology and Tissue Regeneration Work Group, Medical Faculty, Georg-August-University, 37075, Goettingen, Germany aut Monsonego-Ornan Efrat 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 aut Cellular and Molecular Life Sciences Springer Basel 72/3(2015-02-01), 597-615 1420-682X 72:3<597 2015 72 18 https://doi.org/10.1007/s00018-014-1690-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1690-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rais Yoach 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 aut NATIONALLICENCE 700 1- Reich Adi 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 aut NATIONALLICENCE 700 1- Simsa-Maziel Stav 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 aut NATIONALLICENCE 700 1- Moshe Maya 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 aut NATIONALLICENCE 700 1- Idelevich Anna 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 aut NATIONALLICENCE 700 1- Kfir Tal 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 aut NATIONALLICENCE 700 1- Miosge Nicolai Department of Prosthodontics, Oral Biology and Tissue Regeneration Work Group, Medical Faculty, Georg-August-University, 37075, Goettingen, Germany aut NATIONALLICENCE 700 1- Monsonego-Ornan Efrat 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 aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/3(2015-02-01), 597-615 1420-682X 72:3<597 2015 72 18