Osteochondral Cell Fate in the Mandibular Condyle: A Shared Fate Decision Across Development, Degeneration, and...

The mandibular condyle is highly responsive to mechanical loading, which shapes its development and maintains osteochondral homeostasis. Understanding how loading regulates osteochondral cell fate may connect developmental mechanisms with strategies to limit mechanically driven degeneration and promote repair. In this narrative review, we integrate evidence across development, degeneration, and regeneration into a framework centred on a shared cell-fate decision: coordination between progenitor renewal, chondrocyte maturation, and endochondral bone formation. We examine the reported dual modes of parathyroid hormone-related protein (PTHrP) signalling and their interactions with Indian hedgehog (IHH) and canonical Wnt/β-catenin signalling within the broader network governing this balance. Physiological loading supports the spatial and temporal coordination of these pathways, whereas persistent abnormal loading may accelerate hypertrophic differentiation and impair progenitor replenishment, contributing to cartilage damage and aberrant osteochondral remodelling. Effective regeneration may therefore depend on restoring both a favourable mechanical environment and coordinated cell-fate regulation. Accordingly, where pathological occlusal loading contributes to degeneration, correcting the mechanical environment may merit consideration alongside biological interventions tailored to the joint's residual repair capacity. Potential approaches include pathway modulation to support responsive endogenous cells and cell supplementation when progenitor reserves are insufficient.