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46 , 47 HIF in Erythropoiesis Although HIF-1 was first identified as the transcription factor that regulates EPO in human hepatoma cells, in vivo hypoxic stimulation of EPO and erythropoiesis is primarily mediated by HIF-2.48, 49, 50 Its α-subunit was initially described as vascular HIF-1α–like factor (referred to as endothelial PAS domain protein-1), 44 but it was soon realized that HIF-2α was not restricted to endothelial cells

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Common limiting factors Poor microvascular supply: Tendons and ligaments may not receive enough oxygen and nutrients to sustain remodeling Chronic inflammatory signaling: Inflammation may remain dysregulated after the initial stimulus Disorganized collagen remodeling: Tissue repairs, but strength and alignment remain suboptimal Age-related regenerative decline: Older tissues respond less robustly to growth factor signaling Incomplete post-procedure support: Biology is stimulated but not supported long term PRP and prolotherapy light the match