Piezo1 regulates fibrocartilage stem cell in cartilage growth and osteoarthritis

The temporomandibular joint (TMJ) is essential for maxillofacial mechanics, with the condyle serving as the primary site for mandibular growth and development. Mechanical forces regulate condylar development and homeostasis, while aberrant loading contributes to temporomandibular joint osteoarthritis (TMJOA). Although mechanical stimuli are known to influence TMJ function, the role of mechanosensitive ion channels, particularly Piezo1, remains underexplored.

To investigate the role of Piezo1, we performed single-cell ribonucleic acid sequencing (scRNA-seq) on human TMJ samples to assess mechanosensitive ion channel expression. Conditional knockout (CKO) mice were generated using Gli1-Cre^ERT2; Piezo1^fl/fl mice to delete Piezo1 in Gli1+ cells. Unilateral partial discectomy was performed to model TMJOA, followed by histological and immunohistochemical analyses to evaluate the effects of Piezo1 deletion on condylar development and homeostasis.

scRNA-seq revealed high expression of PIEZO1 in both cartilage and bone of the human condyle. Piezo1-tdTomato reporter mice confirmed its consistent expression across different ages. CKO of Piezo1 in Gli1+ cells impaired condylar development and homeostasis by disrupting fibrocartilage stem cell (FCSC) differentiation. In the TMJOA model, Piezo1 deletion mitigated arthritic symptoms, preserved condylar morphology, and reduced cartilage damage.

Piezo1 is a key mechanosensitive ion channel in the cartilage, regulating condylar development and homeostasis. Its deletion in Gli1+ cells disrupts FCSC differentiation and endochondral ossification, leading to developmental deficiencies. However, in pathological conditions, Piezo1 deletion protects against TMJOA, highlighting its potential as a therapeutic target for osteoarthritis prevention and treatment.