Hydrostatic Pressure–Mediated Chondrocyte Homeostasis in Osteoarthritis and Cartilage Engineering

ABSTRACT

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.