Chiaki Tsutsumi-Arai, Amy Tran, Yuki Arai, Wanida Ono, Noriaki Ono
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引用次数: 0
Abstract
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 increases during the early stages of TMJ-OA to promote cell proliferation, but its eventual decrease contributes to the progression of the disease. This highlights the complex role of PTHrP in maintaining MCC homeostasis and its potential involvement in TMJ-OA pathology. The MCC combines the characteristics of growth and articular cartilage and functions distinctively in three phases: development before occlusion, growth after the occlusion is established, and maintenance after the growth is complete. While PTHrP plays a multifaceted role in all phases, further research is needed to fully understand how it regulates MCC development, growth and diseases.
期刊介绍:
Orthodontics & Craniofacial Research - Genes, Growth and Development is published to serve its readers as an international forum for the presentation and critical discussion of issues pertinent to the advancement of the specialty of orthodontics and the evidence-based knowledge of craniofacial growth and development. This forum is based on scientifically supported information, but also includes minority and conflicting opinions.
The objective of the journal is to facilitate effective communication between the research community and practicing clinicians. Original papers of high scientific quality that report the findings of clinical trials, clinical epidemiology, and novel therapeutic or diagnostic approaches are appropriate submissions. Similarly, we welcome papers in genetics, developmental biology, syndromology, surgery, speech and hearing, and other biomedical disciplines related to clinical orthodontics and normal and abnormal craniofacial growth and development. In addition to original and basic research, the journal publishes concise reviews, case reports of substantial value, invited essays, letters, and announcements.
The journal is published quarterly. The review of submitted papers will be coordinated by the editor and members of the editorial board. It is policy to review manuscripts within 3 to 4 weeks of receipt and to publish within 3 to 6 months of acceptance.