Tuwatnawanit T, Wessman W, Belisova D, Sumbalova Koledova Z, Tucker A S, Anthwal N
Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK.
Department of Conservative Dentistry and Prosthodontics, Faculty of Dentistry, Srinakharinwirot University, Wattana, Bangkok, Thailand.
J Dent Res. 2025 May;104(5):551-560. doi: 10.1177/00220345251313795. Epub 2025 Feb 14.
The temporomandibular joint (TMJ) is one of the most used joints in the body. Defects and wear in the cartilage of the joint, condyle, and fibrocartilage disc lie at the heart of many common TMJ disorders. During postnatal development, the condyle acts as a growth center for the mandible, with cells moving as a conveyor belt away from the top of the condyle as they differentiate. The superficial layers of the condyle have been proposed to contain stem/progenitor populations to allow growth and maintain homeostasis. Here we have focused on the role of fibroblast-specific protein 1 (FSP1; also known as S100a4) as a key fibroblast stem/progenitor marker for the condyle. Lineage tracing with mice revealed that FSP1-expressing cells were restricted to the superficial fibroblast zone, giving rise to all layers of the condyle over time. The FSP1-expressing cells overlapped with other putative stem cell markers of the condyle, such as Gli1 and scleraxis. BrdU pulse chase experiments highlighted that a subset of FSP1 fibrocartilage was label retaining, suggesting that FSP1 labels a novel stem/progenitor cell population in the condyle. Destruction of FSP1-expressing cells by conditional diphtheria toxin activity in mice resulted in severe TMJ osteoarthritis with loss of the cartilage structure. Lgr5-expressing cells in the superficial layer of the condyle have been shown to create a Wnt inhibitory niche. FSP1 expression postnatally was associated with a reduction in canonical Wnt activity in the condyle. Importantly, constitutive activation of Wnt/β catenin in FSP1-expressing cells led to a downregulation of FSP1 and progressive postnatal loss of TMJ condylar hyaline cartilage due to loss of the superficial stem/progenitor cells. These data demonstrate a novel role for FSP1-expressing cells in the superficial zone in growth and maintenance of the TMJ condylar cartilage and highlight the importance of regulating Wnt activity in this population.
颞下颌关节（TMJ）是人体中使用最为频繁的关节之一。关节软骨、髁突和纤维软骨盘的缺陷与磨损是许多常见颞下颌关节紊乱症的核心问题。在出生后的发育过程中，髁突作为下颌骨的生长中心，细胞在分化时像传送带一样从髁突顶部移开。有人提出髁突的表层含有干/祖细胞群体，以实现生长并维持体内平衡。在此，我们重点研究了成纤维细胞特异性蛋白1（FSP1；也称为S100a4）作为髁突关键成纤维细胞干/祖细胞标志物的作用。对小鼠进行谱系追踪显示，表达FSP1的细胞局限于表层成纤维细胞区，随着时间推移可形成髁突的所有层次。表达FSP1的细胞与髁突的其他假定干细胞标志物（如Gli1和硬骨素）重叠。BrdU脉冲追踪实验表明，FSP1纤维软骨的一个亚群具有标记保留能力，这表明FSP1标记了髁突中一个新的干/祖细胞群体。通过在小鼠中进行条件性白喉毒素活性实验破坏表达FSP1的细胞，会导致严重的颞下颌关节骨关节炎，同时软骨结构丧失。髁突表层中表达Lgr5的细胞已被证明可形成一个Wnt抑制微环境。出生后FSP1的表达与髁突中经典Wnt活性的降低有关。重要的是，在表达FSP1的细胞中持续激活Wnt/β-连环蛋白会导致FSP1下调，并且由于表层干/祖细胞的丧失，出生后颞下颌关节髁突透明软骨会逐渐丧失。这些数据证明了表层区表达FSP1的细胞在颞下颌关节髁突软骨生长和维持中的新作用，并突出了调节该群体中Wnt活性的重要性。
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