Acupuncture alleviates the progression of knee osteoarthritis by inhibiting X-inactive specific transcript-mediated activation of the mechanosensitive ion channel Piezo1 signaling.

Acupuncture (AP) has been widely used in the treatment of knee osteoarthritis (KOA); however, its underlying molecular mechanisms remain elusive. This study aimed to identify whether acupuncture can relieve KOA progress via inhibiting X-inactive specific transcript (XIST)-mediated Piezo1 activation. The OA cells treated by interleukin (IL)-1β, and rat OA models induced by monosodium iodoacetate were established respectively. The expression of XIST, Piezo1, and extracellular matrix (ECM)-degeneration proteins were evaluated. Cell proliferation was detected by Cell Counting Kit-8 assay. The binding interaction between XIST and Piezo1 was performed using RNA binding protein immunoprecipitation assay (RIP). When XIST is knocked down, apoptosis is significantly reduced, and CHON-001 cell proliferation is increased in comparison to control and IL-1β-induced chondrocytes. Function tests revealed that both in vitro and in vivo, siRNA targeting XIST (si-XIST) increased cell proliferation while preventing apoptosis, ECM degradation, and the production of inflammatory factors. Additionally, we demonstrated that XIST and Piezo1 were bound together via insulin-like growth factor 2 messenger RNA (mRNA) binding proteins 2 (IGF2BP2), with Piezo1 serving as XIST's target. The effects of XIST downregulation were reversed by Piezo1 activation via rescue tests conducted both in vitro and in vivo. Piezo1's expression was reversed after XIST knockdown by IGF2BP2 overexpression. Our findings highlight the therapeutic potential of acupuncture in mitigating the progression of KOA by targeting the XIST-mediated activation of the Piezo1 pathway. By inhibiting this pathway, acupuncture may offer a promising approach to ameliorate the symptoms and slow the progression of KOA.