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. 2022 Feb 15;10:14. doi: 10.1038/s41413-021-00185-7

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Complementary action of serine uptake and synthesis in challenged chondrocytes. Relative serine (Ser; a) and glycine (Gly; b) uptake in cultured chondrocytes derived from wild-type (Phgdh^chon+) and chondrocyte-specific PHGDH knockout (Phgdh^chon−) mice (n = 4–5). c Slc1a4 and Slc6a9 mRNA levels in wild-type and PHGDH-deficient chondrocytes (n = 3). d Growth curve of chondrocytes cultured in complete growth medium or serine/glycine-free medium (n = 3), based on their DNA content. e Proliferation of chondrocytes cultured in complete growth medium or serine/glycine-free medium (n = 3), as evidenced by BrdU incorporation. f Glucose uptake in chondrocytes cultured in complete growth medium or serine/glycine-free medium (n = 4–5). Serine (g) and glycine (h) labeling from ¹³C₆-glucose in chondrocytes cultured in complete growth medium or serine/glycine-free medium (n = 6). Specific mass distribution vectors for each metabolite are shown. i Glut1, Phgdh, Psat1, and Shmt1 mRNA levels in chondrocytes cultured in complete growth medium or serine/glycine-free medium (n = 3). j Intracellular levels of the indicated metabolites in chondrocytes cultured in complete growth medium or serine/glycine-free medium (n = 4-5). R-5-P represents ribose-5-phosphate, Cit represents citrate, αKG represents α-ketoglutarate, Suc represents succinate, Fum represents fumarate, Mal represents malate and Asp represents aspartate. The data are presented as the means ± SDs; *P < 0.05 vs. Phgdh^chon+, **P < 0.01 vs. Phgdh^chon+, ***P < 0.001 vs. Phgdh^chon+ (Student’s t test)