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The raw RNA sequencing data was mapped to human reference genome hg38 using the STAR aligner 63 , and genes annotated in Gencode v36 64 was quantified using featurecounts in the subread package 65

36 Conversely, BMAL1 knockout in chondrocytes ( Col21-CreER, Bmal1 flox/flox ) significantly reduces VEGF and HIF-1 levels while increasing MMP13 and Runx2 expression, ultimately suppressing cell proliferation and promoting apoptosis

Locally produced IGF-1 also contributes to autocrine and paracrine signallingtissues produce their own IGF-1 in response to GH stimulation, creating local high concentrations even when systemic IGF-1 remains modest