Hypoxia‐Driven Regulation of Osteogenic Differentiation in Human Periosteal Stem Cells via the HIF‐1α/miR‐129‐5p/BMP2 Axis

ABSTRACT This study aims to elucidate the regulatory mechanisms of osteogenic differentiation in human periosteal stem cells (hPSCs) under hypoxia, focusing on the HIF‐1α/miR‐129‐5p/BMP2 axis. RNA‐seq identified miRNAs involved in hypoxia‐induced differentiation, and key molecules were validated at molecular and cellular levels. Hypoxia significantly enhanced osteogenic differentiation, as demonstrated by increased mineralization and upregulated osteogenic markers ( BMP2 , RUNX2 , and Osterix ). miR‐129‐5p was downregulated under hypoxia, and its overexpression suppressed BMP2 expression, indirectly affecting HIF‐1α levels and weakening osteogenic differentiation. HIF‐1α was identified as an upstream regulator of these miRNA changes. These findings provide new insights into the role of hypoxia in bone regeneration and offer potential strategies for bone repair and stem cell therapy.