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. 2022 Aug 2;23(15):8592. doi: 10.3390/ijms23158592

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Integrated bidirectional regulation of FGF1 and CCN2 by the FGF signal in chondrocytes. Canonical FGF signaling emitted by FGF-1 induces FOXA1 to activate FGF1 and repress CCN2 simultaneously. Activation of FGF1 results in the formation of a positive feedback loop to amplify the outcome of this bipartite regulation. Synergistic cartilage degeneration would be induced by enhancing the catabolic effects of the FGF signal and repressing the anabolic effects of CCN2. Objects on FGF1 and CCN2 stand for transcriptional co-activator and co-repressor, respectively.