ArticleProceedings of the National Academy of Sciences of the United States of America2014
Cav3.2 T-type calcium channel is required for the NFAT-dependent Sox9 expression in tracheal cartilage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
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- Small molecule inhibition rescues the skeletal dysplasia phenotype of Trpv4 mutant mice.JCI insight · 2026Article
- Tissue Mimetic Membranes for Healing Augmentation of Tendon-Bone Interface in Rotator Cuff Repair.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- TRPC1 links calcium signaling to cellular senescence in the protection against posttraumatic osteoarthritis.JCI insight · 2024Article
- T-Type Voltage-Gated Calcium Channels: Potential Regulators of Smooth Muscle Contractility.International journal of molecular sciences · 2024Review
- The T-Type Calcium Channel CACNA1H is Required for Smooth Muscle Cytoskeletal Organization During Tracheal Tubulogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The T-type calcium channelosome.Pflugers Archiv : European journal of physiology · 2024Review
- Wnt signaling regulates ion channel expression to promote smooth muscle and cartilage formation in developing mouse trachea.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Wnt signaling regulates ion channel expression to promote smooth muscle and cartilage formation in developing mouse trachea.bioRxiv : the preprint server for biology · 2023Article
- Systematic Analysis of Smooth Muscle and Cartilage Ring Formation during Mouse Tracheal Tubulogenesis.Bio-protocol · 2023Article
- Regulation of pain neurotransmitters and chondrocytes metabolism mediated by voltage-gated ion channels: A narrative review.Heliyon · 2023Review
- The temporal transcriptomic signature of cartilage formation.Nucleic acids research · 2023Article
- CaJournal of thrombosis and haemostasis : JTH · 2022Article
- Targeted Activation of G-Protein Coupled Receptor-Mediated CaTissue engineering. Part A · 2022Article
- Neuromedin B promotes chondrocyte differentiation of mesenchymal stromal cells via calcineurin and calcium signaling.Cell & bioscience · 2021Article
- Mammalian tracheal development and reconstruction: insights from in vivo and in vitro studies.Development (Cambridge, England) · 2021Article
- Voltage-Gated Calcium Channels in Nonexcitable Tissues.Annual review of physiology · 2021Review
- Integrating Bioelectrical Currents and CaBioelectricity · 2020Review
- The RCAN1.4-calcineurin/NFAT signaling pathway is essential for hypoxic adaption of intervertebral discs.Experimental & molecular medicine · 2020Article
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
Intracellular Ca(2+) transient is crucial in initiating the differentiation of mesenchymal cells into chondrocytes, but whether voltage-gated Ca(2+) channels are involved remains uncertain. Here, we show that the T-type voltage-gated Ca(2+) channel Cav3.2 is essential for tracheal chondrogenesis. Mice lacking this channel (Cav3.2(-/-)) show congenital tracheal stenosis because of incomplete formation of cartilaginous tracheal support. Conversely, Cav3.2 overexpression in ATDC5 cells enhances chondrogenesis, which could be blunted by both blocking T-type Ca(2+) channels and inhibiting calcineurin and suggests that Cav3.2 is responsible for Ca(2+) influx during chondrogenesis. Finally, the expression of sex determination region of Y chromosome (SRY)-related high-mobility group-Box gene 9 (Sox9), one of the earliest markers of committed chondrogenic cells, is reduced in Cav3.2(-/-) tracheas. Mechanistically, Ca(2+) influx via Cav3.2 activates the calcineurin/nuclear factor of the activated T-cell (NFAT) signaling pathway, and a previously unidentified NFAT binding site is identified within the mouse Sox9 promoter using a luciferase reporter assay and gel shift and ChIP studies. Our findings define a previously unidentified mechanism that Ca(2+) influx via the Cav3.2 T-type Ca(2+) channel regulates Sox9 expression through the calcineurin/NFAT signaling pathway during tracheal chondrogenesis.
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