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

IF 2.4 3区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE
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.

下颌髁突软骨的发育和疾病:以pthrp为中心的观点。
下颌髁突软骨(MCC)是颞下颌关节(TMJ)的双重功能组成部分,作为下颌运动的关节软骨和下颌髁垂直生长的生长软骨。甲状旁腺激素相关蛋白(PTHrP)在协调长骨软骨形成中起关键作用,其在MCC发展和TMJ功能中的重要性也得到强调。在这里,我们讨论PTHrP在MCC的发育、生长和疾病中的作用。PTHrP是MCC中的一个关键形态因子,通过促进软骨细胞增殖和防止过早肥厚分化来调节软骨形成。PTHrP仅在浅层表达,并在MCC中扩散并靶向更深层的软骨细胞,调节RUNX2和SOX9等转录因子。PTHrP调节软骨细胞分化主要通过两种途径:抑制肥大的PTHrP- pth1r信号通路和平衡增殖与肥大的PTHrP- ihh负反馈回路。在出生后小鼠MCC中,PTHrP水平在早期较高,在P21左右开始咀嚼后下降。机械环境的改变,如治疗诱导的下颌骨进展,增加PTHrP表达,促进软骨细胞增殖和延缓肥大。PTHrP在成人TMJ疾病,特别是骨关节炎(OA)中也起双重作用;PTHrP表达在TMJ-OA的早期阶段短暂升高,促进细胞增殖,但其最终降低有助于疾病的进展。这突出了PTHrP在维持MCC稳态中的复杂作用及其在TMJ-OA病理中的潜在参与。MCC结合了生长软骨和关节软骨的特点,在咬合前的发育、咬合建立后的生长和生长完成后的维持三个阶段具有明显的功能。虽然PTHrP在所有阶段都发挥着多方面的作用,但需要进一步的研究来充分了解它如何调节MCC的发育、生长和疾病。
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来源期刊
Orthodontics & Craniofacial Research
Orthodontics & Craniofacial Research 医学-牙科与口腔外科
CiteScore
5.30
自引率
3.20%
发文量
65
审稿时长
>12 weeks
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.
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