Real-time Visualization and Analysis of Chondrocyte Injury Due to Mechanical Loading in Fully Intact Murine Cartilage Explants

Kotelsky, Alexander; Carrier, Joseph S; Buckley, Mark R.

doi:10.3791/58487-v

Cited by 2 publications

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“…To condition the abnormal osteoarthritic environment, mice underwent a noninvasive anterior cruciate ligament injury (ACL-I), the most common joint injury increasing early onset OA [27][28][29][30]. We observed the modulated of Piezo1 and Piezo2 channels post-exercise and post-injury by immunohistochemistry and the mechanical susceptibility of chondrocytes ex vivo using a custom-built mechanical impact device [30][31][32]. This report provides the evidence of the exercise-driven Piezo1 and Piezo2 modulations and essential roles of Piezo1-mediated chondrocyte mechanotransduction in ECM remodeling and chondro-protection.…”

Section: Main Textmentioning

confidence: 99%

“…To confirm the roles of Piezo1 on mechanical susceptibility of chondrocytes in situ, we pretreated femoral cartilage of hindlimb with Yoda1, a Piezo1-specific chemical agonist (Piezo2specific agonists have yet to be discovered). We then quantified the cellular susceptibility against mechanical impact on the femoral head of control mice (female C57BL6/J) ex vivo, as described in [30,31]. The Yoda1-treated group showed a significantly increased area of chondrocyte death compared to the untreated contralateral limbs (Fig.…”

Section: Piezo1 Activation By Yoda1 Increases Chondrocytes' Mechanica...mentioning

confidence: 99%

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Mechano-adaptation: Exercise-driven Piezo1 & Piezo2 augmentation and chondroprotection in articular cartilage

Jing,

Kotelsky,

Zhang

et al. 2024

Preprint

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Chondrocytes in adult joints are mechanosensitive post-mitotic quiescent cells with robustly expressed both Piezo1 and Piezo2 ion channels. Here, we examined the mechano-adaptation and Piezo modulations in articular chondrocytes using a mouse exercise model. We first found differential expression patterns of PIEZO1 and PIEZO2 in articular chondrocytes of healthy knee joints; chondrocytes in tibial cartilage (T) exhibit significantly higher PIEZO1 and PIEZO2 than femoral chondrocytes (F). Interestingly, a few weeks of exercise caused both PIEZO1 and PIEZO2 augmentation in F and T compared to the sedentary control group. Despite the increased expression levels of these mechanosensors, chondrocytes in exercised cartilage exhibit significantly reduced mechanical susceptibility against 1mJ impact. PIEZO1 modulation was relatively more rapid than PIEZO2 channels post-exercise. We tested the exercise-induced effect using Piezo1-conditional knockout (Pz1-cKO; Agc1CreERT2;Piezo1fl/fl). Pz1-cKO mice exhibit diminished exercise-driven chondroprotection against 1mJ impact, suggesting essential roles of Piezo1-mediated mechanotransduction for physiologic-induced cartilage matrix homeostasis. In addition, using a mouse OA model, we further found the modulated PIEZO1 in chondrocytes, consistent with reports in Ren et al., but without PIEZO2 modulations over OA progression. In summary, our data reveal the distinctly tuned Piezo1 and Piezo2 channels in chondrocytes post-exercise and post-injury, in turn modulating the mechanical susceptibility of chondrocytes. We postulate that Piezo1 is a tightly-regulatedbiphasic biomarker; Piezo1 antagonism may increase cellular survival post-injury and Piezo1 (with Piezo2) agonism to promote cartilage ECM restoration.

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Section: Main Textmentioning

confidence: 99%

Section: Piezo1 Activation By Yoda1 Increases Chondrocytes' Mechanica...mentioning

confidence: 99%

Mechano-adaptation: Exercise-driven Piezo1 & Piezo2 augmentation and chondroprotection in articular cartilage

Jing,

Kotelsky,

Zhang

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Effect of knee joint loading on chondrocyte mechano-vulnerability and severity of post-traumatic osteoarthritis induced by ACL-injury in mice

Kotelsky

Elahi

Yigit

et al. 2022

Osteoarthritis and Cartilage Open

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Real-time Visualization and Analysis of Chondrocyte Injury Due to Mechanical Loading in Fully Intact Murine Cartilage Explants

Cited by 2 publications

References 0 publications

Mechano-adaptation: Exercise-driven Piezo1 & Piezo2 augmentation and chondroprotection in articular cartilage

Mechano-adaptation: Exercise-driven Piezo1 & Piezo2 augmentation and chondroprotection in articular cartilage

Effect of knee joint loading on chondrocyte mechano-vulnerability and severity of post-traumatic osteoarthritis induced by ACL-injury in mice

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