دورية أكاديمية

Membrane stretch as the mechanism of activation of PIEZO1 ion channels in chondrocytes.

التفاصيل البيبلوغرافية
العنوان: Membrane stretch as the mechanism of activation of PIEZO1 ion channels in chondrocytes.
المؤلفون: Savadipour A; Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO 63110.; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110.; Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63110.; Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO 63110., Nims RJ; Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO 63110.; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110.; Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO 63110., Rashidi N; Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO 63110.; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110.; Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63110.; Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO 63110., Garcia-Castorena JM; Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO 63110.; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110.; Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO 63110.; Division of Biology and Biomedical Sciences, Biochemistry, Biophysics, and Structural Biology Program, Washington University in St. Louis, St. Louis, MO 63110., Tang R; Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO 63110.; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110.; Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO 63110., Marushack GK; Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO 63110.; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110.; Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO 63110., Oswald SJ; Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO 63110.; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110.; Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO 63110., Liedtke WB; Department of Neurology, Duke University, Durham, NC 27705.; Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010., Guilak F; Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO 63110.; Shriners Hospitals for Children - St. Louis, St. Louis, MO 63110.; Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63110.; Center of Regenerative Medicine, Washington University in St. Louis, St. Louis, MO 63110.; Division of Biology and Biomedical Sciences, Biochemistry, Biophysics, and Structural Biology Program, Washington University in St. Louis, St. Louis, MO 63110.; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63110.
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Jul 25; Vol. 120 (30), pp. e2221958120. Date of Electronic Publication: 2023 Jul 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Chondrocytes*/metabolism , Osteoarthritis*/metabolism, Humans ; Ion Channels/metabolism ; Joints ; Mechanotransduction, Cellular ; Calcium Signaling
مستخلص: Osteoarthritis is a chronic disease that can be initiated by altered joint loading or injury of the cartilage. The mechanically sensitive PIEZO ion channels have been shown to transduce injurious levels of biomechanical strain in articular chondrocytes and mediate cell death. However, the mechanisms of channel gating in response to high cellular deformation and the strain thresholds for activating PIEZO channels remain unclear. We coupled studies of single-cell compression using atomic force microscopy (AFM) with finite element modeling (FEM) to identify the biophysical mechanisms of PIEZO-mediated calcium (Ca 2+ ) signaling in chondrocytes. We showed that PIEZO1 and PIEZO2 are needed for initiating Ca 2+ signaling at moderately high levels of cellular deformation, but at the highest strains, PIEZO1 functions independently of PIEZO2. Biophysical factors that increase apparent chondrocyte membrane tension, including hypoosmotic prestrain, high compression magnitudes, and low deformation rates, also increased PIEZO1-driven Ca 2+ signaling. Combined AFM/FEM studies showed that 50% of chondrocytes exhibit Ca 2+ signaling at 80 to 85% nominal cell compression, corresponding to a threshold of apparent membrane finite principal strain of E = 1.31, which represents a membrane stretch ratio (λ) of 1.9. Both intracellular and extracellular Ca 2+ are necessary for the PIEZO1-mediated Ca 2+ signaling response to compression. Our results suggest that PIEZO1-induced signaling drives chondrocyte mechanical injury due to high membrane tension, and this threshold can be altered by factors that influence membrane prestress, such as cartilage hypoosmolarity, secondary to proteoglycan loss. These findings suggest that modulating PIEZO1 activation or downstream signaling may offer avenues for the prevention or treatment of osteoarthritis.
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معلومات مُعتمدة: F32 AR074240 United States AR NIAMS NIH HHS; P30 AR073752 United States AR NIAMS NIH HHS; R01 AG015768 United States AG NIA NIH HHS; R01 AR072999 United States AR NIAMS NIH HHS; R01 AR080902 United States AR NIAMS NIH HHS; R01 AG046927 United States AG NIA NIH HHS; P30 AR074992 United States AR NIAMS NIH HHS
فهرسة مساهمة: Keywords: cartilage; mechanobiology; mechanosensitive ion channel; mechanotransduction; osteoarthritis
المشرفين على المادة: 0 (Ion Channels)
0 (PIEZO1 protein, human)
تواريخ الأحداث: Date Created: 20230717 Date Completed: 20230719 Latest Revision: 20240118
رمز التحديث: 20240118
مُعرف محوري في PubMed: PMC10372640
DOI: 10.1073/pnas.2221958120
PMID: 37459546
قاعدة البيانات: MEDLINE