Hydrostatic Pressure-Mediated Chondrocyte Homeostasis in Osteoarthritis and Cartilage Engineering

Articular cartilage homeostasis and osteoarthritis (OA) progression are strongly influenced by hydrostatic pressure (HP) within the joint mechanical microenvironment. Physiological-range HP (approximately 0.1-10 MPa in most experimental models) can maintain the chondrocyte phenotype, promote chondrogenic differentiation of stem/progenitor cells, support extracellular matrix (ECM) anabolism, and attenuate inflammatory, oxidative, and apoptotic signaling. By contrast, sustained or high-magnitude HP, particularly ≥20 MPa in injurious in vitro models, commonly shifts cartilage cells toward catabolism and cellular stress. Mechanistically, HP engages wingless-related integration site/β-catenin (Wnt/β-catenin), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), Hippo-Yes-associated protein (Hippo-YAP), noncoding RNA, epigenetic, heat-shock protein, and transient receptor potential (TRP) channel networks. Distinct from earlier reviews focused primarily on chondrogenesis or broad cartilage mechanobiology, this review integrates healthy and OA chondrocytes with progenitor-cell responses, compares HP delivery and culture systems, reconciles apparently contradictory parameter-response data, and evaluates translational opportunities and limitations. These comparisons support evidence-informed starting ranges for future HP protocols, while emphasizing that no single regimen is universally optimal.