Mandibular Condylar Cartilage in Development and Diseases: A PTHrP ‐Centric View

作者：Chiaki Tsutsumi‐Arai, Amy Tran, Yuki Arai, Wanida Ono, Noriaki Ono · 发表于：Orthodontics and Craniofacial Research · 年份：2025 · DOI：10.1111/ocr.12936 · 被引用次数：5 · 研究领域：Bone health and treatments、Osteoarthritis Treatment and Mechanisms、Temporomandibular Joint Disorders

The mandibular condylar cartilage (MCC) is a dual-function component of the temporomandibular joint (TMJ), acting as both articular cartilage for jaw movement and growth cartilage for vertical growth of the mandibular condyle. Parathyroid hormone-related protein (PTHrP) plays a critical role in orchestrating chondrogenesis in the long bone, and its importance is also highlighted in both MCC development and TMJ function. Here, we discuss the role of PTHrP in the development, growth and diseases of the MCC. PTHrP is a key morphogen in the MCC that regulates chondrogenesis by promoting chondrocyte proliferation and preventing premature hypertrophic differentiation. Exclusively expressed in the superficial layer, PTHrP diffuses across the MCC and targets chondrocytes in deeper layers, regulating transcription factors such as RUNX2 and SOX9. PTHrP regulates chondrocyte differentiation through two main pathways: the PTHrP-PTH1R signalling pathway, which suppresses hypertrophy and the PTHrP-Ihh negative feedback loop, which balances proliferation and hypertrophy. In the postnatal murine MCC, PTHrP levels are high early on and decrease after the onset of mastication around P21. Altered mechanical environments, such as those therapeutically induced as mandibular advancement, increase PTHrP expression, promoting chondrocyte proliferation and delaying hypertrophy. PTHrP also plays a dual role in adult TMJ diseases, particularly in osteoarthritis (OA); PTHrP expression transiently increa...