TRPM7 knockdown attenuated CFA-induced rat AA development and protected cartilage destruction and bone erosion by suppressing ferroptosis. (A) Timeline of animal experiment. (B) Representative IVIS images depicting D-luciferin biodistribution in normal and AA rats treated with AAV9 expressing negative control shRNA or with TRPM7 specific shRNA (n = 3 rats). (C) Representative of ankle joints image, H&E staining and safranin O/fast green staining on cartilages. (D) Arthritis swelling severity scores in AA rats (n = 8 rats). (E) Articular cartilage thickness and chondrocyte number in AA rats (n = 3 rats). (F) Representative TEM images of rats in indicated groups (n = 3 rats). Orange triangles indicate mitochondria. (G) Immunostaining of COL2A1, ACSL4, NOX4 and GPX4 in cartilages. White dashed lines indicate the cartilage margin. (H) Micro-CT analysis for the ankles of rats in indicated groups. (I) Representative micro-CT images of the trabecular in bone. (J) Quantitative analysis of bone mineral density (BMD), bone volume to tissue volume (BV/TV), bone surface to tissue volume (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) were measured (n = 3 rats). Data are means ± SEM. *P < 0.05, **P < 0.01 Control KD + AA versus Control KD; #P < 0.05, ##P < 0.01 TRPM7 KD + AA versus Control KD + AA. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)