ESPEYB18 5. Bone, Growth Plate and Mineral Metabolism Advances in skeletal biology (5 abstracts)
5.14. Piezo1 inactivation in chondrocytes impairs trabecular bone formation
Gretl Hendrickx , Verena Fischer , Astrid Liedert , Simon von Kroge , Melanie Haffner-Luntzer , Laura Brylka , Eva Pawlus , Michaela Schweizer , Timur Yorgan , Anke Baranowsky , Tim Rolvien , Mona Neven , Udo Schumacher , David J Beech , Michael Amling , Anita Ignatius & Thorsten Schinke
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Bone Miner Res. 2021 Feb;36(2):369–384 Abstract: https://pubmed.ncbi.nlm.nih.gov/33180356/
In brief: Chondrocyte-specific ablation of the mechano-sensory Piezo1 results in substantially impaired formation of secondary spongiosa during endochondral bone formation. The study explores this unexpected finding and show that mechano-sensing in growth plate chondrocytes directly regulates the formation of bone trabeculae in the secondary spongiosa.
Comment: Osteocytes are considered to be the main mechano-sensors in bone. Nevertheless, the distinct mechanisms of mechanical sensing and the role of other skeletal cells and tissues is still subject to research. Recently, the mechano-sensing ion channel Piezo1 was shown to activate Wnt1 signal pathway as well as to induce Akt phosphorylation to increase bone formation (1).
Here, Hendrickx et al. investigated the role of Piezo1 and Piezo2 in different skeletal cells from conditional knock-out mice. Unexpectedly, knockout in Runx2 expressing cells (intended to target osteoprogenitors and early osteoblasts) showed a more severe phenotype than osteocyte-specific knockout. The authors further observed pronounced structural impairments in the trabecular compartment adjacent to the growth plate. Pursuing these findings, they found that Runx2-expressing growth plate chondrocytes, not the targeted osteoblast progenitors, were responsible for the bone phenotype.
The unexpected and novel finding is that growth plate chondrocytes are mechano-sensory cells that regulate formation of trabecular bone. This opens a new perspective on the role of the transient growth plate cartilage in bone formation. The bone trabeculae formed during endochondral bone formation at the growth plates fuse with cortical bone and thereby make substantial contributions to the strength of the newly formed bone (2). It therefore makes sense that mechano-sensing in growth plate chondrocytes can regulate the formation of the secondary spongiosa. This study, taken together with the study of Xie et al. (see paper 5.16), point to the importance of hypertrophic chondrocytes as a potential key cell to transfer mechanical stress cues to the newly formed bone during endochondral bone formation.
Reference: 1. Xu, X., et al., Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone. Int J Mol Sci, 2021. 22(12).2. Cadet, E.R., et al., Mechanisms responsible for longitudinal growth of the cortex: coalescence of trabecular bone into cortical bone. J Bone Joint Surg Am, 2003. 85(9): p. 1739–48.
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