Hypoxic Conditions Modulate Chondrogenesis through the Circadian Clock : The Role of Hypoxia-Inducible Factor-1α

Juhász, Krisztián Zoltán and Hajdú, Tibor and Kovács, Patrik and Vágó, Judit and Matta, Csaba and Takács, Roland (2024) Hypoxic Conditions Modulate Chondrogenesis through the Circadian Clock : The Role of Hypoxia-Inducible Factor-1α. CELLS, 13 (6). p. 512. ISSN 2073-4409

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Abstract

Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor composed of an 11 alpha and a beta subunit. HIF-1 is a master regulator of cellular response to hypoxia by activating 12 transcription of genes that facilitate metabolic adaptation to hypoxia. Since chondrocytes in mature 13 articular cartilage reside in a hypoxic environment, HIF-1α plays an important role in chondrogen- 14 esis and in the physiological lifecycle of articular cartilage. Accumulating evidence suggest interac- 15 tions between the HIF pathways and the circadian clock. Although the circadian clock is an emerg- 16 ing regulator in both developing and mature chondrocytes, how circadian rhythm is established 17 during the early steps of cartilage formation and through what signaling pathways it promotes the 18 healthy chondrocyte phenotype is still not entirely known. This narrative review aims to deliver a 19 concise analysis of the existing understanding of the dynamic interplay between HIF-1α and the 20 molecular clock in chondrocytes, both in states of health and disease, while also incorporating cre- 21 ative interpretations. We explore diverse hypotheses regarding the intricate interactions among 22 these pathways and propose relevant therapeutic strategies for cartilage disorders such as osteoar- 23 thritis.

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