Osteoarthritis (OA), the leading cause of disability, is driven by articular cartilage degeneration and inflammation. Mechanosensitive ion channels PIEZO1 and PIEZO2 have been implicated in OA progression via calcium signaling in chondrocytes. This study investigates the role of conditional Piezo channel knockout (cKO) in modulating calcium signaling and senescence in OA, particularly under the supra-physiologic inflammatory condition of a high-fat diet (HFD). Using calcium imaging, we found that Piezo1 cKO and dual Piezo1/2 cKO significantly reduced Yoda1-induced calcium signaling, while Piezo2 cKO alone had no effect. Under HFD conditions, Piezo1 cKO showed a non-significant trend toward reduced calcium influx, potentially due to high inflammatory burden or altered Piezo1 expression. Immunohistochemical analysis revealed that Piezo1 cKO significantly attenuated expression of the senescence marker p16, even under HFD conditions, suggesting downstream protective effects. In contrast, p21 expression patterns were inconsistent and appeared influenced by metabolic or stress-related vi pathways outside of senescence. These findings identify Piezo1 as a key contributor to OA related mechanotransduction and senescence, supporting its potential as a therapeutic target and warranting further investigation into combinatorial strategies for OA intervention.
","abstract_html":"<p>Osteoarthritis (OA), the leading cause of disability, is driven by articular cartilage degeneration and inflammation. Mechanosensitive ion channels PIEZO1 and PIEZO2 have been implicated in OA progression via calcium signaling in chondrocytes. This study investigates the role of conditional Piezo channel knockout (cKO) in modulating calcium signaling and senescence in OA, particularly under the supra-physiologic inflammatory condition of a high-fat diet (HFD). Using calcium imaging, we found that Piezo1 cKO and dual Piezo1/2 cKO significantly reduced Yoda1-induced calcium signaling, while Piezo2 cKO alone had no effect. Under HFD conditions, Piezo1 cKO showed a non-significant trend toward reduced calcium influx, potentially due to high inflammatory burden or altered Piezo1 expression. Immunohistochemical analysis revealed that Piezo1 cKO significantly attenuated expression of the senescence marker p16, even under HFD conditions, suggesting downstream protective effects. In contrast, p21 expression patterns were inconsistent and appeared influenced by metabolic or stress-related vi pathways outside of senescence. These findings identify Piezo1 as a key contributor to OA related mechanotransduction and senescence, supporting its potential as a therapeutic target and warranting further investigation into combinatorial strategies for OA intervention.</p>","abstract_has_math":false,"creators":["Paradi, Sophie Gretler"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Thesis","degree_discipline":"Biomedical Engineering","degree_department":null,"school":null,"contributors":["Dr. Farshid Guilak","Dr. Spencer Lake Dr. Jessica Wagenseil"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-05-07T07:00:00Z","date_published":"2025-05-07T07:00:00Z","updated_at":"2026-07-24T06:12:58Z","subjects":["osteoarthritis","orthopedics","piezo","mechanotransduction","obesity","senescence","knee","OA","Biomedical Engineering and Bioengineering"],"languages":["English (en)"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://openscholarship.wustl.edu/eng_etds/1202"],"render_values":[{"text":"https://openscholarship.wustl.edu/eng_etds/1202","href":"https://openscholarship.wustl.edu/eng_etds/1202","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.7936/ey8g-wf84","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dr. Farshid Guilak","Dr. Spencer Lake Dr. Jessica Wagenseil"]},{"key":"dc:creator","label":"Author","values":["Paradi, Sophie Gretler"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2025-05-01T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Engineering","McKelvey School of Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["osteoarthritis","orthopedics","piezo","mechanotransduction","obesity","senescence","knee","OA","Biomedical Engineering and Bioengineering"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English (en)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.7936/ey8g-wf84","https://openscholarship.wustl.edu/eng_etds/1202"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Osteoarthritis (OA), the leading cause of disability, is driven by articular cartilage degeneration and inflammation. Mechanosensitive ion channels PIEZO1 and PIEZO2 have been implicated in OA progression via calcium signaling in chondrocytes. This study investigates the role of conditional Piezo channel knockout (cKO) in modulating calcium signaling and senescence in OA, particularly under the supra-physiologic inflammatory condition of a high-fat diet (HFD). Using calcium imaging, we found that Piezo1 cKO and dual Piezo1/2 cKO significantly reduced Yoda1-induced calcium signaling, while Piezo2 cKO alone had no effect. Under HFD conditions, Piezo1 cKO showed a non-significant trend toward reduced calcium influx, potentially due to high inflammatory burden or altered Piezo1 expression. Immunohistochemical analysis revealed that Piezo1 cKO significantly attenuated expression of the senescence marker p16, even under HFD conditions, suggesting downstream protective effects. In contrast, p21 expression patterns were inconsistent and appeared influenced by metabolic or stress-related vi pathways outside of senescence. These findings identify Piezo1 as a key contributor to OA related mechanotransduction and senescence, supporting its potential as a therapeutic target and warranting further investigation into combinatorial strategies for OA intervention.
"]},{"key":"dc:title","label":"Title","values":["The Role of Piezo1 in Mediating Chondrocyte Cell Signaling and Senescence"]}]}],"canonical_facts":{"dc:contributor":["Dr. Farshid Guilak","Dr. Spencer Lake Dr. Jessica Wagenseil"],"dc:creator":["Paradi, Sophie Gretler"],"dc:date.available":["2025-05-01T07:00:00Z"],"dc:description.abstract":["Osteoarthritis (OA), the leading cause of disability, is driven by articular cartilage degeneration and inflammation. Mechanosensitive ion channels PIEZO1 and PIEZO2 have been implicated in OA progression via calcium signaling in chondrocytes. This study investigates the role of conditional Piezo channel knockout (cKO) in modulating calcium signaling and senescence in OA, particularly under the supra-physiologic inflammatory condition of a high-fat diet (HFD). Using calcium imaging, we found that Piezo1 cKO and dual Piezo1/2 cKO significantly reduced Yoda1-induced calcium signaling, while Piezo2 cKO alone had no effect. Under HFD conditions, Piezo1 cKO showed a non-significant trend toward reduced calcium influx, potentially due to high inflammatory burden or altered Piezo1 expression. Immunohistochemical analysis revealed that Piezo1 cKO significantly attenuated expression of the senescence marker p16, even under HFD conditions, suggesting downstream protective effects. In contrast, p21 expression patterns were inconsistent and appeared influenced by metabolic or stress-related vi pathways outside of senescence. These findings identify Piezo1 as a key contributor to OA related mechanotransduction and senescence, supporting its potential as a therapeutic target and warranting further investigation into combinatorial strategies for OA intervention.
"],"dc:identifier":["https://doi.org/10.7936/ey8g-wf84","https://openscholarship.wustl.edu/eng_etds/1202"],"dc:language":["English (en)"],"dc:subject":["osteoarthritis","orthopedics","piezo","mechanotransduction","obesity","senescence","knee","OA","Biomedical Engineering and Bioengineering"],"dc:title":["The Role of Piezo1 in Mediating Chondrocyte Cell Signaling and Senescence"],"thesis:degree_discipline":["Biomedical Engineering","McKelvey School of Engineering"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T06:12:58Z"}