Reduced mitochondrial biogenesis capacity and function in human osteoarthritis (OA) chondrocytes. (a) PGC-1α, acetyl-lysine PGC-1α, expression of mitochondrial transcriptional factor A (TFAM), nuclear respiratory factor 1 (NRF-1), and NRF-2 in normal donor and human OA chondrocyte lysates, as determined by Western blotting. (b) Expression of mitochondrial respiratory complexes I–IV and ATP synthase (complex V) in normal and OA chondrocytes, as determined by Western blotting. (c) Top, Mitochondrial DNA (mtDNA) content as determined by the mtDNA-encoded cytochrome c oxidase subunit I or II (COX1 or COX2): nucleus-encoded 18S ribosomal DNA (18S rDNA) ratio. Bottom, Mitochondrial mass, as determined by MitoTracker Green FM staining. Values are the mean ± SD and are from a representative experiment of five independent experiments performed using chondrocytes from five different pairs of normal and OA (grade III or IV) donors. Original magnification × 10. (d) Oxygen consumption rate (OCR) (top) and intracellular ATP level (bottom) in normal and OA chondrocytes. Values are the mean ± SD of 3 independent experiments performed using chondrocytes from 3 different pairs of normal and OA (grade III or IV) donors. Results in a and c are representative of experiments using chondrocytes from 5 different pairs of normal and OA (grade III or IV) donors. nDNA = nuclear DNA. (This figure is reproduced from ref. 6 with permission from John Wiley & Sons)