Fig. 8. LDHA inhibition is efficacious in human articular chondrocytes.

Medial and lateral cartilage samples were obtained from knee articular cartilage of patients undergoing TKA (n = 12). Medial regions of articular cartilage were more severely damaged upon radiographic and visual analysis by surgeon, while lateral regions were healthier regions of cartilage with little signs of OA. a–d LDHA, G6PD2, MMP13, and NFKBIZ gene expression was measured in OA cartilage by qPCR. Gene expression was normalized to actin. Gene expression is displayed as fold change in medial cartilage sample relative to paired lateral cartilage sample. Bars represent mean ± S.D. for n = 12 patient samples. e, f Primary human knee articular chondrocytes were treated with IL-1β (10 ng/mL) for 24 h. Seahorse was performed to measure ECAR and OCR as previously stated. Bars represent mean ± S.D. for five wells. Data is representative of one out of two experiments. g IHC was performed for IκB-ζ in healthy and OA human cartilage (arrows). Representative images of n = 3 samples are displayed. h–j Chondrocytes were isolated from human knee articular cartilage. Cells were treated with IL-1β (10 ng/mL) for 24 h in the presence or absence of IKK2i (10 μM) or FX11 (40 μM). Gene expression of NFKBIZ, IL-6, and MMP13 was measured by qPCR, with bars representing mean of technical duplicates. Results are representative of one out of two independent experiments with similar trends. a–d Two-tailed student’s t-test was performed. p-values indicated in figure.